Name: 1211441-98-3|7-Cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide|98%
Brand: Ambeed
SKU: A288696
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Yield	Reaction Conditions	Operation in experiment
36%	With tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate; In 1,4-dioxane; at 100℃; for 1h;Microwave irradiation;	General procedure: A mixture of 5-[4-(2,2,2-trifluoro-ethyl)-piperazin-1-yl]-pyridin-2-ylamine (158 mg, 0.607 mmol), 2-chloro-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide (118 mg, 0.405 mmol), Pd2(dba)3 (18.5 mg, 0.020 mmol), BINAP (25 mg, 0.040 mmol) and sodium-tert-butoxide (70 mg, 0.728 mmol) in dioxane (3.5 mL) is degassed and heated to 100 C. for 1 h in a CEM Discover microwave. The reaction mixture is partitioned between dichloromethane and saturated NaHCO3 solution. The organic layer is separated and the aqueous layer extracted with further dichloromethane. The combined organics are ished with brine, dried (MgSO4), filtered and concentrated. The crude product is purified using silica gel chromatography (0 to 10% methanol/dichloromethane) to give 7-cyclopentyl-2-{5-[4-(2,2,2-trifluoro-ethyl)-piperazin-1-yl]-pyridin-2-ylamino}-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide, which is purified further by trituration with acetonitrile (115 mg, 55%). MS(ESI) m/z 517.2 (M+H)+ (method A). 1H NMR (400 MHz, Me-d3-OD): 8.72 (1H, s), 8.24 (1H, d), 7.98 (1H, d), 7.50 (1H, dd), 6.62 (1H, s), 4.81-4.72 (1H, m), 3.27-3.09 (12H, m), 2.89 (4H, t), 2.61-2.49 (2H, m), 2.16-2.01 (4H, m), 1.81-1.69 (2H, m).

2
[ 1211441-98-3 ]
[ 108-24-7 ]
[ 1211440-39-9 ]

Yield	Reaction Conditions	Operation in experiment
91%	In dichloromethane; for 0.166667h;	<strong>[1211441-98-3]7-cyclopentyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide</strong> (30 mg, 0.230 mmol) in 5 mL of dichloromethane. Added 0.5 mL of acetic anhydride. After 10 min, reaction is complete and trituration with acetonitrile gave 2-[5-(4-acetyl- piperazin-1-yl)-pyridin-2-ylamino]-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide (30 mg, 91%). MS(ESI) m/z 411.3 (M+H)+

Reference： [1]Patent: WO2010/20675,2010,A1 .Location in patent: Page/Page column 107; 108

3
[ 1211441-98-3 ]
[ 4023-34-1 ]
[ 1211440-87-7 ]

Yield	Reaction Conditions	Operation in experiment
68%	With triethylamine; In dichloromethane; at 20℃; for 18h;	To a solution of 7-cyclopentyl-2-(5-piperazin-l -yl-pyridin-2-ylamino)-7H-pyrrolo[2,3-d]pyrimidine- 6-carboxylic acid dimethylamide (100 mg, 0.230 mmol) and cyclopropanecarbonyl chloride (22 mL, 0.690 mmol) in 5 mL OfCH2Cl2 is added a solution OfEt3N (64 mL, 0.459 mmol) and stirred at rt for 18 h. The resulting mixture is concentrated and diluted with saturated NaHCO3 and extracted with ethyl acetate (3x100 mL). The combine organics are dried over Na2CO3 and preparative HPLC to give 2-[5-(4-carbamoylmethyl-piperazin-1-yl)-pyridin-2-ylamino]-7-cyclopentyl-7H-pyrrolo[2,3- d]pyrimidine-6-carboxylic acid dimethylamide (81 mg, 68%). MS(ESI) m/z 503.3 (M+H)+

Reference： [1]Patent: WO2010/20675,2010,A1 .Location in patent: Page/Page column 108

4
[ 74-96-4 ]
[ 1211441-98-3 ]
[ 1211442-07-7 ]

Yield	Reaction Conditions	Operation in experiment
63%	With potassium carbonate; In tetrahydrofuran; at 70℃;	To a solution of 7-cyclopentyl-2-(5-piperazin-l -yl-pyridin-2-ylamino)-7H-pyrrolo[2,3-d]pyrimidine- 6-carboxylic acid dimethylamide (100 mg, 0.229 mmol) in 20 mL of THF is added potassium carbonate (100 mg, 0.689 mmol) then bromoethane (75 mg, 0.687 mmol). The reaction mixture is heated at 70 C for 18 h. Following SiO2 chromatography, eluting with 0-10% (2M NH3 in MeOH)/dichloromethan] gave 7-cyclopentyl-2-[5-(4-ethyl-piperazin-1-yl)-pyridin-2-ylamino]-7H pyrrolo[2,3d]pyrimidine-6-carboxylic acid dimethylamide (67 mg, 63%). MS(ESI) m/z 463.3 (M+H)+

Reference： [1]Patent: WO2010/20675,2010,A1 .Location in patent: Page/Page column 93

5
[ 1211441-98-3 ]
[ 15448-47-2 ]
[ 1211441-56-3 ]

Yield	Reaction Conditions	Operation in experiment
16%	In ethanol; at 70℃; for 18h;	To a solution of 7-cyclopentyl-2-(5-piperazin-l -yl-pyridin-2-ylamino)-7H-pyrrolo[2,3-d]pyrimidine- 6-carboxylic acid dimethylamide (55 mg, 0.123 mmol) and (R)-2-methyl-oxirane (250 mg, 4.3 mmol) in 5 mL of ethanol is heated at 70 C for 18 h. Following SiO2 chromatography, eluting with 0-10% (2M NH3 in MeOH)/dichloromethane] gave 7-cyclopentyl-2-{5-[4-((R)-2-hydroxy-propyl)- piperazin-1-yl]-pyridin-2-ylamino}-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide (10 mg, 16%). MS(ESI) m/z 493.3 (M+H)+ 1H NMR (400 MHz, CDCl3): 8.70 (1H, s), 8.32 (1H, d), 7.96 (1H, s), 7.80 (1H, s), 7.28 (1H, d), 6.45 (1H, s), 5.32 (1H, s), 4.86-4.77 (1H, s), 3.85 (2H, t), 3.44 (2H, t), 3.18 (6H, s), 2.98 (3H, s), 2.62- 2.59 (2H, m), 2.11-2.02 (3H,m); 1.74-1.63 (3H, m)

Reference： [1]Patent: WO2010/20675,2010,A1 .Location in patent: Page/Page column 95; 96

6
[ 1211441-98-3 ]
[ 67-64-1 ]
[ 1211441-71-2 ]

Yield	Reaction Conditions	Operation in experiment
61%	With sodium tris(acetoxy)borohydride; In dichloromethane; at 20℃; for 18h;	To a solution of 7-cyclopentyl-2-(5-piperazin-l -yl-pyridin-2-ylamino)-7H-pyrrolo[2,3-d]pyrimidine- 6-carboxylic acid dimethylamide (30 mg, 0.069 mmol) in 10 mL of dichloromethane is added 1 mL of acetone and NaB(OAc)3H (30 mg, 0.138 mmol). The resulting mixture is stirred at room temperature for 18 h. Following purification by preparative LCMS gave 7-cyclopentyl-2-[5-(4- isopropyl-piperazin-1-yl)-pyridin-2-ylamino]-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid diethylamide (20 mg, 61%). MS(ESI) m/z All 3 (M+H)+

Reference： [1]Patent: WO2010/20675,2010,A1 .Location in patent: Page/Page column 101; 102

7
[ 1003-03-8 ]
[ 1211441-98-3 ]

Reference： [1]Patent: US2012/115878,2012,A1
[2]Patent: CN106749259,2017,A
[3]Patent: CN106928236,2017,A
[4]Patent: CN107936029,2018,A
[5]Patent: US2019/345163,2019,A1

8
[ 110-15-6 ]
[ 1211441-98-3 ]
7-cyclopentyl-N,N-dimethyl-2-[5-(piperazin-1-yl)pyridin-2-yl]amino}-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide succinate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
94.9%	In isopropyl alcohol; at 27 - 83℃;Inert atmosphere;	A nitrogen-flushed, 1 L, 4-neck, round bottom flask is charged with 11.16 g (0.0945 mol, 1.05 eq.) of succinic acid (A5), and 245 g (312 mL) of 2-propanol. The suspension is stirred and warmed to 65±3 C. to obtain a clear solution. The solution is filtered while warmed through glass-fiber filter paper. The filtrate is held at 30±3 C. for addition to A4. A nitrogen-flushed 2 L, 4-neck, round bottom flask is charged with 39.11 g (0.09 mol, 1.0 eq) of 7-cyclopentyl-N,N-dimethyl-2-(5-(piperazin-1-yl)pyridin-2-ylamino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (A4) and 1115 g (1420 mL) of 2-propanol. The resulting suspension is stirred and heated to 80±3 C. to obtain a hazy yellow solution. The solution is cooled to 70±3 C. and filtered through a 25 g pad of Celite. The warm, filtered A4 solution is transferred to a nitrogen-flushed, 3 L, Argonaut reactor system and re-heated to 80±3 C. The succinic acid/2-propanol solution is added over 1 h maintaining 80±3 C. throughout the addition. The batch is seeded after 80% of the succinic acid solution has been added. The sample is stirred at 80±3 C. for 1 h after the addition is completed and cooled to 20±3 C. over 1 h, held 30 minutes and the solids are filtered. The filter cake is washed with 78 g (100 mL) of 2-propanol. The solids are dried at 60 C. for at least 16 h or until the LOD is 1% to afford 47.16 g (94.9%, corrected) of Compound A6 as a yellow, crystalline solid, mp 202-203 C.
78.7%	In water; acetone; at 0 - 50℃;Flow reactor; Inert atmosphere;	In a glove box under inert atmosphere (nitrogen), a solution of succinic acid (0.8 g) in water (9.6 mL) was prepared at 50 C (solution A). Ribociclib base (2.8 g) was charged in a 100 mL reactor. Solution A was added to Ribociclib base. The mixture was further diluted with water (10 mL), then succinic acid (0.72 g) was added to the mixture affording complete dissolution. Water was then distilled under vacuum to a residual volume of 10 mL at 50 C. Acetone (56 mL) was added at 50 C and precipitation was observed after addition of about 30 mL of acetone. The suspension was then cooled down to 0 C in 1 h and kept under stirring at 0 C for 30 min. The solid was isolated by filtration and washed with acetone (10 mL). Ribociclib succinate was dried under vacuum at 50 C for 18 h (2.8 g, 78.7% yield, 99.04%) purity).

Reference： [1]Patent: US2012/115878,2012,A1 .Location in patent: Page/Page column 12
[2]Patent: WO2019/40567,2019,A1 .Location in patent: Page/Page column 20-23; 26-27

9
[ 571188-59-5 ]
[ 1211441-98-3 ]

Reference： [1]Patent: US2012/115878,2012,A1
[2]Patent: CN109400612,2019,A
[3]Patent: WO2019/82143,2019,A1
[4]Patent: WO2019/82143,2019,A1

10
[ 571189-16-7 ]
[ 1211441-98-3 ]

Reference： [1]Patent: US2012/115878,2012,A1
[2]Patent: CN106749259,2017,A
[3]Patent: WO2019/82143,2019,A1
[4]Patent: WO2019/82143,2019,A1

11
[ 733039-20-8 ]
[ 1211441-98-3 ]

Reference： [1]Patent: US2012/115878,2012,A1
[2]Patent: CN107936029,2018,A
[3]Patent: CN108586356,2018,A
[4]Patent: CN108586356,2018,A
[5]Patent: CN108586356,2018,A

12
[ 1211443-61-6 ]
[ 1211441-98-3 ]

Reference： [1]Patent: US2012/115878,2012,A1
[2]Patent: CN107936029,2018,A
[3]Patent: CN108586356,2018,A
[4]Patent: CN109400612,2019,A
[5]Patent: WO2019/142206,2019,A1

13
[ 1374639-76-5 ]
[ 1211441-98-3 ]

Reference： [1]Patent: US2012/115878,2012,A1
[2]Patent: WO2018/51280,2018,A1

14
[ 1374639-77-6 ]
[ 1211441-98-3 ]

Reference： [1]Patent: US2012/115878,2012,A1
[2]Patent: WO2018/51280,2018,A1

15
[ 1374639-78-7 ]
[ 1211441-98-3 ]

Yield	Reaction Conditions	Operation in experiment
98.8%	With phosphoric acid; In dichloromethane;	The above-obtained intermediate 7-cyclopentyl-N,N-dimethyl-2-[5-(4-tert-butoxycarbonylpiperazin-1-yl)pyrazolePyridin-2-yl]amino}-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (IX) (5.353 g, 10 mmol) is dissolved in 30 ml of dichloromethanThe alkane solution was added with 15 ml of hydrochloric acid (2 mol/L) and stirred at room temperature for 1 h. The reaction was stopped and then distilled under reduced pressure. The resulting concentrate was dissolved in 5 ml of ethyl acetate, and the organic phase was washed with saturated sodium bicarbonate to pH. 7-8, the aqueous phase was extracted twice with ethyl acetate, and the organic phases were combined, dried over anhydrous sodium sulfate, and distilled under reduced pressure. The resulting concentrate was recrystallized with n-hexane and vacuum dried to give Rebsini (a white solid product). X) 4.26 g; Yield 98.0%; Purity 99.8% (HPLC area normalization method); (6) Preparation of Rebocini (X)The difference with Example 1 is that the acid used is phosphoric acid.The final white solid product, rebamizin (X) 4.32 g; yield 98.8%; purity 99.8% (HPLC areaNormalization);
95.7%	With hydrogenchloride; In tetrahydrofuran; at 35 - 40℃; for 4h;	In a 500 ml four-necked flask,Add 200 grams of 15% hydrogen chloride in tetrahydrofuran solution,26.8 g (0.05 mol) of N,N-dimethyl-7-cyclopentyl-2-{5-[(4-tert-butoxycarbonylpiperazin-1-yl)pyridin-2-yl]amino-7H Pyrrole [2,3-d]pyrimidine-6-carboxamide (prepared in step (2)),The reaction was carried out at 35-40 C for 4 hours, and the liquid phase detection reaction was completed.Hydrogen chloride tetrahydrofuran solution is distilled off under reduced pressure (after adding hydrogen chloride to the required concentration, it can be used in the next batch of reaction),To the residue was added 100 g of water, 8.0 g of potassium carbonate, filtered, and the filter cake was washed with 50 g of ethanol and dried.Obtained 20.8 g of white solid Rebsini,The liquid phase purity was 99.9%, and the yield was 95.7%.
93%	With hydrogenchloride; In water; toluene; at 0 - 20℃; for 2.5h;	A solution of 1N HCl (6.0 eq) was added to the compound of Formula (2-A) (10.44 g, 1.0 eq) in toluene (105 mL) at 0 to 5 C., and the mixture was stirred at room temperature for 2.5 hours. Following this time, the mixture was extracted with 1N HCl (2×40 mL), and the pH of the aqueous phase was adjusted to 1112 by charging aqueous NaOH (20 wt %). The resulting precipitate was collected by filtration to afford Ribociclib (1) (7.95 g, 93% yield) as a yellow solid having HPLC purity of 97%.

91.1%	With hydrogenchloride; In water; at 20 - 30℃;	Tert-butyl 4-(6- { [7-cyclopentyl-6-(dimethylcarbamoyl)-7H-pyrrolo[2, 3-d]pyrimidin-2-yl]amino } pyridin-3 -yl)piperazine- 1 -carboxylate (100g) was added to the solution of distilled water (200 ml) and conc. HC1 (250 ml) and stirred at 20-30C. The reaction mass was slowly added into pre-chilled aq. NaOH at 0-10C. Isopropyl alcohol (200 ml) and dichloromethane (500 ml) was added to the reaction mixture. The organic layer was concentrated under vacuum and to theresidue was added dichloromethane (100ml) and heptane (500ml). The mixture was stirred at 20-30C. The solid was filtered and dried under vacuum at 60-70C and collected as off-white to pale yellow solid.Yield: 91.1.0 %; HPLC Purity: 99.89%?H NMR (400 MHz DMSO) ppm 9.34-9.3 1 (br,1H), 8.77 (s, 1H), 8.18-8.15 (d,J=9.2, 1H), 8.03-8.02 (d, J=2.8, 1H), 7.46-7.43(dd, J=2.8, J=9.2 , 1H), 6.59 ( s,1H), 4.77- 4.69 (m, 1H), 3.05-3.01 (m, 10 H), 2.84 (m, 4H), 2.43 (m, 2H), 2.19 (m, 1H), 1.97 (m, 4H), 1.64-1.63 (m, 2H)
91%	With hydrogenchloride; water; at 25 - 45℃;	DM water (200.0 mL) and tert-butyl 4-[6-[[7-cyclopentyl-6-(dimethyl carbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]-3-pyridyl]piperazine-l-carboxylate (40.0g, 0.075 moles) were charged into 1L 4N RB flask at 30±5C and stirred for 5- (0137) 10 min. to get cream colored suspension. Reaction mass was heated to 40-45C and diluted aq.hydrochloric acid (199.0 mL, 0.561 moles, prepared by diluting 49.0 mL of Cone hydrochloric acid with 150 mL of DM water) was added dropwise to the above reaction mass and stirred for about lh to get pale brown colored clear solution. Resulting clear solution was further stirred for l-2h for reaction completion. (0138) After reaction completion (by HPLC), reaction mass was diluted with DM water (80 mL) and stirred for 5-l0min. Reaction mass was washed with ethyl acetate (200 mL x 2) and layers were separated. Aqueous layer was basified using aq.sodium hydroxide solution (45. Og of sodium hydroxide was dissolved in 900.0 mL of DM water) and stirred the resulting cream colored suspension for lh at 25-35 C. Product was filtered under suction with the help of DM water (200 mL). Wet product was leached from DM water (400 mL) followed by methanol (200 mL) and product was filtered and dried in hot air oven for 6h at 70-75C. Weight of the product: 29.6g (91.0% by theory). Purity by HPLC > 99.0%.
90%	With hydrogenchloride; In methanol; water; at 10 - 25℃;	tert-butyl 4-(6-((7-cyclopentyl-6-(dimethylaminoformyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperazine-1-carboxylate (53.47g, 100mmol) and methanol (267mL) were added to a three-neck flask. stirred uniformly, cooled to 10 ~ 15 C, added dilute hydrochloric acid (4mol / L, 267mL), after heating, The reaction is carried out at 20 to 25 C for 3 to 4 hours. At the end of the reaction, a part of methanol was rotated, and methyl t-butyl ether (267 mL) was added for At the end of the reaction, a part of methanol was rotated, and methyl t-butyl ether (267 mL) was added for extraction once.The collected aqueous phase was cooled to 0-10 C, dichloromethane (267 mL) was added, 20% sodium hydroxide solution was added dropwise to adjust the pH to 12-13, and the aqueous phase was extracted twice with dichloromethane (133 mL). The organic phase was washed twice with saturated brine (267 mL), concentrated, and then isopropyl alcohol and water were beaten.The solid was isolated by filtration and dried in vacuo to give the product ribociclib (39.11 g, 90%).
85%		In a 1 L four-necked flask was added 20 g of 4-(6-(7-cyclopentyl-6-(dimethylaminoformyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)aminopyridine- 3-yl) piperazine-1-carboxylic acid tert-butyl ester) (formula 3), 100g of n-hexane, stirred and dissolved, dripped at room temperature100 g of 3 mol/L hydrochloric acid was added, and the reaction was carried out for 1 hour, and the liquid layer was separated, and 200 g of acetone was added to the aqueous layer. Warming up to reflux, then loweringThe crystals were warmed to below 10 C, stirred for 3 hours, and filtered to obtain Rebsini hydrochloride.Example 3 Preparation of Rebizzini (Formula 4)Dissolve Rebsini hydrochloride in 200g water, add 1g activated carbon, 0.5g 100~200 mesh column chromatography silica gel, stirDecolorization by adsorption, filtration, adding saturated sodium bicarbonate solution to the filtrate to adjust the pH to 9-10, precipitate solids, cool down to 10Stir at C. After filtration, the cake was dried at 60 C to obtain 14 g of Rebizzini (formula 4) in a yield of 85.0%.
83.7%	With hydrogenchloride; In water; toluene; at 20℃; for 2h;	In a 250 ml round bottom flask,Was added 2-chloro-7-cyclopentyl--N, N- dimethyl--7H- pyrrolo [2,3-d] pyrimidine-6-carboxamide and 14.6g (50mmol),Tert-Butyl 4- (6-aminopyridin-3-yl) piperazine-1-carboxylate15.3 g (55 mmol),0.67 g (3 mmol) of Pd (OAc) 2,BINAP 1.2 g (2 mmol),Cs2CO3 65.1g (200mmol) and 130ml 1,4-dioxane, warmed to 90 C, the reaction was stirred for 8 hours,The reaction was monitored, concentrated under reduced pressure and flash column chromatographyA solution of 4- (6- (7- (dimethylcarbamoyl) -7H-pyrrolo [2,3-d] pyrimidin- 2-ylaminopyridin-3-yl) - carboxylic acid tert-butyl ester.The above obtained solution of 4- (6- (7- (dimethylcarbamoyl) -7H-pyrrolo [2,3-d] pyrimidin- 2-ylaminopyridin-3-yl) - carboxylic acid tert-butyl esterDissolved in 100ml of toluene,Add 30ml 6mol / L hydrochloric acid, and stirred at room temperature for 2 hoursThe reaction was monitored completely, adjusted to pH 8 with sodium hydroxide, extracted with methylene chloride, washed with brine and driedThe organic phase was dried over sodium sulfate, concentrated under reduced pressure,N-hexane to obtain Ribociclib 18.2g, the yield was 83.7%
81%	With hydrogenchloride; In ethanol; water; at 20℃; for 4h;	4- [6-[(7-cyclopentyl) -6-[(dimethylamino) carbonyl] -7H-pyrrolo [2,3] pyrimidin-2-yl] amino]- 3-pyridyl] -1-piperazinecarboxylic acid 1,1-dimethylethyl ester (10.7 g, 0.02 mol) was dissolved in 200 ml of ethanol,10 ml of 3N hydrochloric acid was added, and the reaction was stirred at room temperature for 4 h.After the reaction, 10% sodium hydroxide aqueous solution was added dropwise to adjust the pH of the reaction solution to 8-9, ethanol was distilled off under reduced pressure, and a pale yellow solid was obtained by suction filtration.Acetone was recrystallized to give 7.0 g of a white solid, yield: 81%.
66.1%	With hydrogenchloride; water; In acetone; at 50℃; for 2.16667h;Inert atmosphere;	Under inert atmosphere, tert-butyl 4-(6-(6-(dimethylcarbamoyl)-7-cyclopentyl-7H- pyrrolo[2,3-d]pyrimidin-2-ylamino)pyridin-3-yl)piperazine-l-carboxylate (40.0 g) was suspended in 3 : 1 water/acetone mixture (800 mL) and the suspension was heated to 50 C. Aq. hydrochloric acid 6 M (60.8 mL) was added dropwise in 10 min and the mixture was kept under stirring at 50 C for 2 h. At the end of reaction, the solution was cooled down to 25 C and filtrated on a dicalite pad. Aq. 10%> sodium hydroxide (136 mL) was added dropwise in 10 min and the suspension was kept under stirring for 30 min. Ribociclib base was isolated by filtration, washed with water (120 mL) and dried under vacuum at 20 C for 16 h. Ribociclib was obtained as a solid (66.1% yield).
		A nitrogen-flushed, 3 L Argonaut reactor system is charged with 67.4 g (0.126 mol, 1.0 eq.) of tert-Butyl 4-(6-(7-cyclopentyl-6-(dimethylcarbamoyl)-7H-pyrrolo[2,3-d]pyrimidin-2-ylaminopyridin-3-yl)piperazine-1-carboxylate (A3) and 329 g (380 mL) of toluene. The suspension is stirred and cooled to 12±3 C. 138 g (126 mL, 6.0 eq) of 6N aqueous hydrochloric acid is added over 30 min maintaining a batch temperature 15±3 C. The resulting 2-phase solution is warmed to 25±3 C. and held at this temperature for 30 min or until the remaining starting material, A3, is 2% (area normalization) as determined by HPLC analysis. The progress of the reaction is checked using the Process Steering Control. 250 g (250 mL) of 1N aqueous hydrochloric acid is added and mixture is stirred for 5 min. The 2-phase reaction mixture is filtered through 25 g of filter cel. The phases are separated. The aqueous phase (containing product) is charged to a 2 L, 4-neck, round bottom flask (equipped as described under Apparatus entry 4) and cooled to 15±3 C. The pH is adjusted to 3.2±0.3 with the slow addition of 62 g (41 mL) of 50% aqueous sodium hydroxide, a batch temperature?27±3 C. is maintained throughout the addition. 16.4 g of Si-Thiol functionalized silica gel is added. The slurry is stirred for 3 hours at 50±3 C. The resin is filtered off, the flask and filter cake are rinsed with 50 mL of water. The wash is combined with the filtrate. The filtrate is transferred back to the flask and 16.4 g of Si-Thiol functionalized silica gel is added. The slurry is stirred for 3 hours at 50±3 C. The silica gel is filtered off. The flask and filter cake are rinsed with 50 mL of water. The wash is combined with the filtrate. The filtrate is transferred back to the flask and again 16.4 g of Si-Thiol functionalized silica gel is added. The slurry is stirred for 3 hours at 50±3 C. The silica gel is filtered off. The flask and filter cake are rinsed with 50 mL of water. The wash is combined with the filtrate. A nitrogen-flushed, 3 L, Argonaut reactor system is charged with the filtrate and cooled to 15±3 C. The pH is adjusted to 12.5±0.5 with the slow addition of 17 g (18 mL) of 50% aqueous sodium hydroxide to precipitate the product (Batch volume=900 mL, Max Vol). The sample is stirred for at least 6 h at 22±3 C. The solids are filtered through a polypropylene filter pad. The filter cake is washed four times with 340 g (4*85 mL) of water until the pH of the wash is ?9. The solids are dried at 60 C. for at least 16 h or until the LOD is ?1% to afford 45.7 g (84.9%, corrected) of compound A4 as a tan solid, mp 194-195 C.
	With hydrogenchloride; In water; ethyl acetate; for 10h;	(11) 300 mg of the compound of formula (13) was dissolved10 ml of ethyl acetate,Add 5ml concentrated hydrochloric acid,Reaction for 10 hours,After the reaction is complete,Adding the extractant and water extraction to remove the impurities dissolved in the organic phase,Add sodium bicarbonate to the water phase to alkaline,place,Precipitate pure product7-cyclopentyl--N, N- dimethyl-2 - ((5- (piperazin-1-yl)Pyridin-2-yl) amino) -7H-pyrrolo [2,3-d]Pyrimidine-6-carboxamide(Compound of formula (a))
35.1 g	With hydrogenchloride; In water; toluene; at 10 - 30℃; for 1.16667h;	A solution of tert-butyl 4-(6-((7-cyclopentyl-6-(dimethylcarbamoyl)-7H-pyrrolo[2,3- d]pyrimidin-2-yl)amino)pyridin-3-yl)piperazine-l-carboxylate (Ila) (50 g) in toluene (300 mL) was cooled to 10 C. Hydrochloric acid (6N, 100 mL) was added to the above solution in drop wise at 15 C. The reaction mass was stirred for 1 hour at 25-30 C. Hydrochloric acid (IN, 200 mL) was added to the above reaction mass at 25-30 C and stirred for 10 minutes at the same temperature. The reaction mass was then filtered and washed with toluene (1 x 50 mL) followed by hydrochloric acid (IN, 50 mL). Organic layer was separated and aqueous layer was cooled to 15 C. pH of aqueous layer was adjusted to pH=12.0-12.5 using saturated solution of sodium hydroxide (50% w/w) and stirred for 1 hour at 15-20 C. The resulted precipitate was then filtered, washed with water (3 chi 80 mL) and dried at 50 C for 6 hours to provide the title compound. (0169) Yield: 35.1 g; Purity by HPLC: 99.31 %
	With hydrogenchloride; In water; at 8℃;	In a nitrogen environment at about 25±2 C., mix 2-chloro-7-cyclopentyl-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carbamide and 4-(6-aminopyyrol-3-yl)piperazin-1-carboxyl tert-butylate into tetrahydrofuran THF) added with lithium bis(trimethyl)amine (LiHMDS) and stir for about 1 h to obtain the intermediate 4-[6-[[7-cyclopentyl-6-[(dimethylamino)carbonyl]-7H-pyrrolo[2,3-pyrimidine-2-yl]amino]-3-pyridine]-1-piperazinecarboxyl 1,1-dimethylethylate. Cool the mixture to about 8±2 C. and keep the mixture at this temperature while an aqueous hydrogen chloride solution is subsequently added slowly and mixed into the mixture. After that, using a separatory funnel and ethyl acetate as an extracting agent, perform an extraction process in duplicate to acquire the aqueous phase. When the extracted solution is cooled to about 5 C. or lower, slowly add an aqueous sodium hydroxide solution until the pH reaches 12.5. Heat the solution to 25 C. and stir for about 16 h. Next, filter the solution to obtain the solid matter (or filter cake), and rinse the filter cake with DD water until the pH of the rinsing liquid is equal to or lower than 9. Lastly, dry the filter cake at about 55±5 C. to yield yellowish brown solids, which are 7-cyclopentyl-N,N-dimethyl-2-[5-(piperazin-1-yl)pyridin-2-yl]amino}-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide, whose molar recovery rate can be 98% or higher, with 98% or higher purity.

Reference： [1]Patent: CN107936029,2018,A .Location in patent: Paragraph 0047; 0061-0062; 0078-0079; 0094-0096
[2]Patent: CN109928975,2019,A .Location in patent: Paragraph 0087; 0092-0095; 0096; 0101-0102; 0103
[3]Patent: US2019/345163,2019,A1 .Location in patent: Paragraph 0214-0215
[4]Patent: WO2019/82143,2019,A1 .Location in patent: Page/Page column 42; 43
[5]Patent: WO2019/142206,2019,A1 .Location in patent: Page/Page column 21
[6]Patent: CN108586356,2018,A .Location in patent: Paragraph 0120; 0121
[7]Patent: CN109400612,2019,A .Location in patent: Paragraph 0035-0054
[8]Patent: CN106928236,2017,A .Location in patent: Paragraph 0054; 0055; 0056; 0058; 0059; 0060
[9]Patent: CN110407841,2019,A .Location in patent: Paragraph 0042; 0111-0116
[10]Patent: WO2019/40567,2019,A1 .Location in patent: Page/Page column 23
[11]Patent: US2012/115878,2012,A1 .Location in patent: Page/Page column 11-12
[12]Patent: CN106749259,2017,A .Location in patent: Paragraph 0031; 0066; 0120; 0132; 0144-0149
[13]Patent: WO2018/51280,2018,A1 .Location in patent: Page/Page column 21
[14]Patent: WO2019/82143,2019,A1
[15]Patent: US10336763,2019,B1 .Location in patent: Page/Page column 5

16
[ 606143-89-9 ]
[ 1211441-98-3 ]
C₂₃H₃₀N₈O*C₁₇H₁₅BrF₂N₄O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In water; acetonitrile; at 50℃;	26.6 mg of MEK 162 and 4 mL of acetonitrile / water (v: v = 19: 1) were stirred at 50 C for 30 minutes, 16.0 mg of LEE011 was added, stirring was continued overnight and the temperature was slowly cooled to 20 C and the solid was collected.

Reference： [1]Patent: CN105732642,2016,A .Location in patent: Paragraph 0101; 0102; 0103; 0104; 0105; 0106

17
[ 849217-48-7 ]
[ 1211441-98-3 ]
7-cyclopentyl-2-((5-(4-(1-((4-fluorophenyl)carbamoyl)cyclopropane-1-carbonyl)piperazin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
77%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 12h;	To a two-necked flask, 2d (268 mg, 1.2 mmol), LEE011 (435 mg, 1 mmol), EDCI (288 mg, 1.5 mmol), HOBt (162 mg, 1.2 mmol), DIEA (259 mg, 2 mmol) and DMF (10 mL) were charged. The mixture was stirred at room temperature for 12 hours, then quenched by water. The mixture was extracted by ethyl acetate, and the combined organic layers were washed by saturated aqueous NaHCO3 solution, water and brine, dried by anhydrous magnesium sulphate. The solvent was evaporated, and the residue was purified by silica gel column chromatography to obtain 493 mg (77%) of 12 as a yellow solid. 1H NMR (400 MHz, DMSO-d6) delta 9.70 (d, J = 28.0 Hz, 2H), 8.80 (s, 1H), 8.19 (d, J = 9.1 Hz, 1H), 8.05 (d, J = 3.0 Hz, 1H), 7.62 (ddt, J = 7.1, 5.1, 3.0 Hz, 2H), 7.44 (dd, J = 9.2, 3.0 Hz, 1H), 7.12 (t, J = 8.9 Hz, 2H), 6.60 (s, 1H), 4.73 (p, J = 8.8 Hz, 1H), 3.67 (br, 4H), 3.25 - 2.94 (m, 10H), 2.42 (d, J = 11.0 Hz, 2H), 2.00 - 1.91 (m, 4H), 1.70 - 1.54 (m, 2H), 1.44 - 1.38 (m, 2H), 1.31 - 1.23 (m, 2H); 13C NMR (101 MHz, DMSO) delta 170.78, 168.72, 167.06, 163.32, 160.02, 157.63, 155.14, 152.59, 151.61, 147.00, 142.35, 136.62, 135.45, 135.42, 132.33, 126.35, 123.33, 123.25, 115.57, 115.35, 112.95, 112.26, 101.09, 60.22, 57.42, 49.15, 35.00, 30.91, 30.16, 24.65, 21.21, 14.54, 14.43. ESI-HRMS m/z calcd for C34H39FN9O3+ 640.3154, found 640.3163 [M + H]+. HPLC purity 99%.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 3231 - 3237

18
[ 148256-82-0 ]
[ 1211441-98-3 ]

Reference： [1]Patent: CN106749259,2017,A
[2]Patent: CN108623599,2018,A

19
[ 89479-61-8 ]
[ 1211441-98-3 ]

Reference： [1]Patent: CN106749259,2017,A
[2]Patent: CN108623599,2018,A
[3]Patent: CN108586356,2018,A
[4]Patent: CN108586356,2018,A
[5]Patent: CN108586356,2018,A
[6]Patent: CN108586356,2018,A

20
N-cyclopentyl-N-(5-formyl-2-(methylthio)pyrimidin-4-yl)glycine ethyl ester [ No CAS ]
[ 1211441-98-3 ]

Reference： [1]Patent: CN106749259,2017,A
[2]Patent: CN108623599,2018,A

21
7-cyclopentyl-2-(methylthio)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid [ No CAS ]
[ 1211441-98-3 ]

Reference： [1]Patent: CN106749259,2017,A

22
7-cyclopentyl-N,N-dimethyl-2-(methylthio)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide [ No CAS ]
[ 1211441-98-3 ]

Reference： [1]Patent: CN106749259,2017,A

23
[ 571188-59-5 ]
7-cyclopentyl-N,N-dimethyl-2-(methylsulfonyl)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide [ No CAS ]
[ 1211441-98-3 ]

Yield	Reaction Conditions	Operation in experiment
65%		To a 500 ml round bottom flask was added 16.8 g of compound 7 (50 mmol).18.4 g of compound 8 (60 mmol) was dissolved in 350 ml of toluene and refluxed. After the reaction was completed,The solvent was evaporated under reduced pressure and the residue was dissolved in methanol (300 ml).Adding dilute hydrochloric acid to room temperature reaction,After the reaction is completed, it is alkalized to pH>10 with dilute aqueous ammonia, extracted with ethyl acetate, and washed with saturated brine.Dried over anhydrous sodium sulfate and concentrated to give a white solid compound.The target product after recrystallization (1) 14 g, 65%.

Reference： [1]Patent: CN108623599,2018,A .Location in patent: Paragraph 0015; 0059; 0060
[2]Patent: CN106749259,2017,A

24
[ 39856-50-3 ]
[ 1211441-98-3 ]

Reference： [1]Patent: CN106749259,2017,A
[2]Patent: WO2019/82143,2019,A1
[3]Patent: WO2019/82143,2019,A1
[4]Patent: WO2019/82143,2019,A1
[5]Patent: WO2019/82143,2019,A1

25
[ 5909-24-0 ]
[ 1211441-98-3 ]

Reference： [1]Patent: CN106749259,2017,A

26
[ 1044145-59-6 ]
[ 1211441-98-3 ]

Reference： [1]Patent: CN106749259,2017,A

27
[ 3946-32-5 ]
[ 1211441-98-3 ]
8-[4-(6-[7-cyclopentyl-6-(dimethylcarbamoyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl]amino}pyridin-3-yl)piperazin-1-yl]-8-oxooctanoic acid methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
48%	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 4h;	Add to 50 mL two bottles 7-cyclopentyl-N, N-dimethyl-2 - [[5- (1-piperazinyl) -2-pyridine] amino] -7H-pyrrole [2,3-d] Amide (200 mg, 0.46 mmol), DMF 2 mL, monomethyl maleate (109 mg, 0.55 mmol), N, N-diisopropylethylamine (132 mg, 0.69 mmol) And EDCI (134 mg, 0.69 mmol) were added and stirred at room temperature for 4 hours. After completion of the reaction, 100 mL of ethyl acetate was added, diluted with 100 mL of ethyl acetate, washed successively with saturated aqueous sodium bicarbonate, water and saturated brine. The organic phase was dried over anhydrous magnesium sulfate, filtered to remove the organic solvent, and the residue was purified by column chromatography Brown solid 134. 5 mg, yield = 48%.

Reference： [1]Journal of Medicinal Chemistry,2018,vol. 61,p. 3166 - 3192
[2]Patent: CN106831780,2017,A .Location in patent: Paragraph 0019

28
[ 1211441-98-3 ]
2-((5-(4-(4-aminobutyl)piperazin-1-yl)pyridin-2-yl)amino)-7-cyclopentyl-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide trifluoroacetic acid [ No CAS ]

Reference： [1]Patent: WO2017/185031,2017,A1
[2]Patent: WO2020/23480,2020,A1

29
[ 1211441-98-3 ]
7-cyclopentyl-2-(5-(4-(4-(2-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-ylamino)acetamido)butyl)piperazin-1-yl)pyridin-2-ylamino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide [ No CAS ]

Reference： [1]Patent: WO2017/185031,2017,A1
[2]Angewandte Chemie - International Edition,2019,vol. 58,p. 6321 - 6326
Angew. Chem.,2019,vol. 131,p. 6387 - 6392,6
[3]Patent: WO2020/23480,2020,A1

30
[ 1211441-98-3 ]
[ 164365-88-2 ]
tert-butyl (4-(4-(6-((7-cyclopentyl-6-(dimethylcarbamoyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-1-yl)butyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	With potassium carbonate; potassium iodide; In acetone;Reflux;	To a solution 7-cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide(Rebociclib, 2-13) (19.6 mg, 0.045 mmol) in acetone (0.5 mL) was added tert-butyl 4-bromobut lcarbamate (2-2, 1 7.2 mg, 0.068 mmol), followed by K2CO3 (12.3 mg, 0.09 mmol) and Kl (1 1.3mg, 0.068 mmol) and the resulting mixture was then heated to reflux and stirred overnight. The reaction mixture was diluted with EtOAc and H2O, extracted, and washed with brine. The organic layer was dried over anhydrous Na2S04, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel (0-10% MeOH in DCM) to give Boc protected amine 2-14 as a yellow solid (23.5 mg, 86%). LCMS : m/z 606.4 [M+l]
86%	With potassium carbonate; potassium iodide; In acetone;Reflux;	To a solution of 7-cyclopentyl-N,N-dimethyl-2-(5-(piperazin-1-yl)pyridin-2-ylamino)-7H-pyrrolo[2,3-d\|pyrimidine-6-carboxamide (Rebociclib, 2-13) (19.6 mg, 0.045 mmol) in acetone (0.5 mL) was added <strong>[164365-88-2]tert-butyl 4-bromobutylcarbamate</strong> (2-2, 17.2 mg, 0.068 mmol), followed by K2C3 (12.3 mg, 0.09 mmol) and KI (1 l 3 mg, 0.068 mmol) and the resulting mixture was then heated to reflux and stirred overnight. The reaction mixture was diluted with EtOAc and H2O, extracted, and washed with brine. The organic layer was dried over anhydrous NaiSGy filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel (0-10% MeOH in DCM) to give Boc protected amine 2-14 as a yellow solid (23.5 mg, 86%). LCMS: m/z 606.4 [M+l]

Reference： [1]Patent: WO2017/185031,2017,A1 .Location in patent: Page/Page column 94; 95
[2]Patent: WO2020/23480,2020,A1 .Location in patent: Page/Page column 94
[3]Angewandte Chemie - International Edition,2019,vol. 58,p. 6321 - 6326
Angew. Chem.,2019,vol. 131,p. 6387 - 6392,6

31
2-chloro-4-(cyclopentylamino)pyrimidine [ No CAS ]
[ 1211441-98-3 ]

Reference： [1]Patent: CN106928236,2017,A

32
3-bromo-2-oxo-N,N-dimethylpropanamide [ No CAS ]
[ 1211441-98-3 ]

Reference： [1]Patent: CN106928236,2017,A
[2]Patent: US2018/93950,2018,A1

33
[ 110-15-6 ]
[ 1211441-98-3 ]
7-cyclopentyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide hemi succinate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In ethanol; at 20℃; for 12h;	10.5 mg of compound I freebase was added into ethanol, and 3.0 mg of succinic acid was added, then stirred at room temperature for 12 hours until solids precipitate out. Hemi-succinate Form A was analyzed by XRPD, DSC, TGA and ?H NMR. The XRPD data of the hemi-succinate Form A produced in this example is listed in Table 1. The DSC data shows an endothermic peak at 180 C. (onset temperature). The TGA data shows 12.5% weight loss up to 118 C. The XRPD pattern is displayed in FIG. 1, the ?H NMR spectrum is displayed in FIG. 2. ?H NMR data of hemi-succinate FormAproduced in this example is shown as following: ?H NMR (400 MHz, DMSO) oe 9.29 (s, 1H), 8.76 (s, 1H), 8.16 (d, J=9.0 Hz, 1H), 8.00 (d, J=2.9 Hz, 1H), 7.44 (dd, J=9.2, 3.0 Hz, 1H), 6.60 (s, 1H), 3.15-2.93 (m, 14H), 2.32 (s, 2H), 1.98 (s, 4H), 1.65 (s, 2H)

Reference： [1]Patent: US2017/342075,2017,A1 .Location in patent: Paragraph 0130; 0131; 0132

34
[ 110-15-6 ]
[ 1211441-98-3 ]
7-cyclopentyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide succinate salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
97.1%	In tetrahydrofuran; at 25 - 70℃;	Tetrahydrofuran (120 mL) and Ribociclib (3.0g, 0.0069 moles) were charged into 250 mL 4 neck round bottomed flask at 30±5C and stirred for 5-10 min. to get cream colored suspension. Reaction mass was heated to 65-70C and stirred for 15 min to get clear solution. The solution of succinic acid (0.85g, 0.0072moles) in tetrahydrofuran (60 mL) was added to the above reaction mass dropwise through addition funnel at 65-70C. After addition of succinic acid solution, pale yellow coloured suspension was formed in the reaction mass and was stirred for lh. Then the reaction mass was cooled to 25-35C and stirred for lh. Product was filtered off under suction. Product was dried in vacuum oven at 65-70C to afford title compound as cream coloured solid. Weight of the product: 3.7g (97.1% by theory) as cream coloured solid. Purity by HPLC > 99.0%. (0115) The obtained crystalline compound is characterized by PXRD as illustrated in figure- 1.
95%	In isopropyl alcohol; at 85℃; for 0.5h;	dd 100g of Rebizzini (Formula 4), 1200g of isopropanol to a 2L three-necked flask, heat to 85 C, while 28.53gSuccinic acid was added to 240 g of isopropanol and dissolved by heating. Then, a succinic acid/isopropanol mixed solution was added dropwise to a 2 L three-necked flask.After the addition is completed, a large amount of solid is precipitated, stirred for 30 minutes, naturally cooled to room temperature, stirred for 2 to 3 hours, filtered, and used less.The mixture was washed with cold isopropanol and dried under reduced pressure at 60 C for 24 hours. Resino succinate (Formula 5) dry product 120g, yield 95.0%, byThe purity by HPLC (area normalization method) was 99.91%, the maximum single impurity was 0.06%, and the palladium residue was 0.2 ppm.
90%	In methanol; dichloromethane; at 20 - 30℃;	Method-1 Ribociclib (2 g) and succinic acid (600 mg) were added in the solution of dichloromethane (30 mL) and methanol (10 mL) at 20-30C. Reaction mixture was stirred for 5 0-60 mm followed by addition of diisopropyl ether (20 mL) at the same temperature. The reaction mixture was stirred for 4-5 hrs. The solid soformed, was collected by filtration and dried to give Ribociclib succinate form-N (2.3g).Yield: 90%; HPLC Purity: 99.76%

	In methanol; acetonitrile; at 50℃; for 48h;	10141] 30.7 mg of the non-hydrate form (prepared according to patent CN103201275A) was added into 2.2 mL of acetonitrile/methanol (v/v=10/1), then stirred at 50 C. for 48 hours, until solids precipitate out.The XRPD data of the mono-succinate Form Iproduced in this example is listed in Table 4 and the XRPDpattern was displayed in FIG. 5.The ?H NMR spectrum of the mono-succinateForm I produced in this example is displayed in FIG. 6. ?HNMR data is shown as following: ?H NMR (400 MHz, DM50) oe 9.33 (s, 1H), 8.76(s, 1H), 8.16 (d, J=9.1 Hz, 1H), 8.00 (d, J=2.9 Hz, 1H), 7.45(dd, J9.1, 3.0 Hz, 1H), 6.60 (s, 1H), 4.79-4.68 (m, 1H),3.16-3.00 (m, 14H), 2.34 (s, 4H), 1.98 (s, 4H), 1.64 (d, J=5.5Hz, 2H). ?H NMR results show that Form I is a monosuccinate of compound I.DSC curve of mono-succinate Form I was displayed in FIG. 7. Form I is an anhydrate, the DSC data showed an endothermic peak at 197 C. (onset temperature).TGA curve of mono-succinate Form I was displayed in FIG. 8. The TGA data showed 2.0% weight loss up to 178 C
435 mg	In isopropyl alcohol; at 25 - 75℃; for 16h;	Ribociclib free base (500 mg) was added to iso-propanol (30 mL) and stirred at 75C for 25 minutes to obtain a reaction mixture. Iso-propanol (2.5 mL) with succinic acid (150 mg) was added to the reaction mixture and stirring was continued at 75C for 4 hours. Iso-propanol (10 mL) was again added to the reaction mixture and the mixture was stirred at ambient temperature for 12 hours to obtain a solid. The solid obtained wascollected by filtration and then dried at 50C under vacuum for 10 hours to obtain the titlecompound. Yield: 435 mg
1.2 g	In water; at 25 - 55℃;	Succinic acid (0.285 g, 0.0024mol) was charged into a reaction flask containing water (5.0 rnL) at 25-30C. Reaction mass was heated to 50-55C. Charged Ribociclib base (1.0 g, 0.0023mol) at 50-55C and stirred for 2hours minutes at 50-55C. Reaction mass filtered through 0.22 micron filter and washed with water (2.0 mL). Concentrated the reaction mass under vacuum at 65-70C with Heptane, isolated the product. Dried the material under vacuum at 55-60C for 12- 15 hours.Yield: 1.2 g.
	In 1,4-dioxane; at 25 - 30℃; for 4h;	To a suspension of ribociclib base (1.0 g) in l,4-dioxane (30ml) was added succinic acid (0.28g ) at 25-30C. The reaction mixture was stirred at 25-30C for 4 hr. The solids were isolated by filtration and dried at 50C under vacuum, resulted the title compound (T l5g) and identified by XRD as Form-C2, as presented in figure 1.
	In isopropyl alcohol;	Weigh 5.0mg succinic acid in 1.0mL isopropanol, weigh 20.0mg of compound (I) suspended in 1.0mL isopropanol,A solution of succinic acid in isopropanol was added dropwise, filtered, and the filter cake was dried in vacuum at 40 C to obtain a solid.

Reference： [1]Patent: WO2019/142206,2019,A1 .Location in patent: Page/Page column 16-17
[2]Patent: CN109400612,2019,A .Location in patent: Paragraph 0055-0057
[3]Patent: WO2019/82143,2019,A1 .Location in patent: Page/Page column 43; 44
[4]Patent: US2017/342075,2017,A1 .Location in patent: Paragraph 0141; 0142; 0143; 0144; 0145; 0146; 0147
[5]Patent: WO2019/111160,2019,A1 .Location in patent: Page/Page column 2; 14; 15
[6]Patent: WO2019/123364,2019,A1 .Location in patent: Page/Page column 15; 16
[7]Patent: WO2019/167068,2019,A1 .Location in patent: Page/Page column 33
[8]Patent: CN110964017,2020,A .Location in patent: Paragraph 0151-0153

35
[ 124-04-9 ]
[ 1211441-98-3 ]
7-cyclopentyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide adipate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In water; acetone; at 20℃;	200mg of compound I freebase powder was addedinto 10.0 mL of acetone/water (v/v=19/1), and 68 mg of adipic acid was added to the solution, then stirred at room temperature, the solid was obtained. The ?H NMR spectrum is displayed in FIG. 22.?H NMR data of adipate Form A produced in this example is shown as following: ?H NMR (400 MHz, DMSO) oe 9.31 (s, 1H), 8.76 (s, 1H), 8.15 (d, J=9.1 Hz, 1H), 7.99 (d, J=2.8 Hz, 1H), 7.42 (dd, J=9.1, 3.0 Hz, 1H), 6.60 (s, 1H), 4.78-4.67 (m, 1H), 3.06 (d, J=4.9 Hz, 1OH), 2.95-2.82 (m, 4H), 2.48-2.38 (m, 2H), 2.25-2.09 (m, 4H), 1.98 (s, 4H), 1.64 (d, J=4.9 Hz, 2H),1.54-1.38 (m, 4H). The result shows the solid is adipate Form A. The XRPD data of the adipate Form A produced in this example are listed in Table 7. The XRPD pattern is displayed in FIG.13, the DSC curve is displayed in FIG. 14, the TGA curve is displayed in FIG. 15.

Reference： [1]Patent: US2017/342075,2017,A1 .Location in patent: Paragraph 0151; 0152; 0153; 0154; 0155; 0156; 0157

36
[ 1211441-98-3 ]
[ 110-16-7 ]
7-cyclopentyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide maleate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In water; acetone; at 20℃;	200.63 mg of compound I freebase powder was added into 10.0 mE of acetone/water (v/v=1 9/1), and 56 mg of maleic acid was added to the solution, then stirred at room temperature, the solid was obtained, The ?H NMR spectrum is displayed in FIG. 23.?H NMR data of the maleate Form A produced in this example are shown as following:?H NMR (400 MHz, DMSO) oe 9.49 (s, 1H), 8.77 (s, 1H), 8.20 (d, J=9.1 Hz, 1H), 8.07 (d, J=2.8 Hz, 1H), 7.52 (dd, J=9.1, 2.8 Hz, 1H), 6.62 (s, 1H), 6.04 (s, 2H), 4.80-4.66 (m, 1H), 3.34 (d, J=5.6 Hz, 4H), 3.28 (d, J=5.3 Hz, 4H), 3.06 (s, 6H), 2.48-2.35 (m, 2H), 1.98 (s, 4H), 1.65 (d, J=5.3 Hz, 2H).The result shows the solid is maleate Form A. The XRPD data of the maleate Form A is listed in Table 9. The XRPD pattern is displayed in FIG. 16, the DSC curve is displayed in FIG. 17, the TGA curve is displayed in FIG. 18

Reference： [1]Patent: US2017/342075,2017,A1 .Location in patent: Paragraph 0158; 0159; 0160; 0161; 0162; 0163

37
[ 79-14-1 ]
[ 1211441-98-3 ]
[ 110-15-6 ]

Yield	Reaction Conditions	Operation in experiment
	In water; acetone; at 20℃;	199.0 mg of compound I freebase powder was added into 10.0 mL of acetone/water (v/v=19/1), and 34.0 mg of glycolic acid was added to the solution, then stirred at room temperature, the solid was obtained. The H?NMR spectrum is displayed in FIG. 24.?H NMR data of glycollate Form A produced inthis example is shown as following:?H NMR (400 MHz, DM50) oe 9.09 (d, J=10.7 Hz,1H), 8.53 (s, 1H), 7.93 (d, J=9.1 Hz, 1H), 7.78 (d, J=2.9 Hz,1H), 7.21 (dd, J=9.1, 2.9 Hz, 1H), 6.37 (s, 1H), 4.55-4.45 (m,1H), 3.54 (s, 2H), 2.95-2.87 (m, 4H), 2.83 (s, 6H), 2.79-2.74(m, 4H), 2.24-2.17 (m, 2H), 1.75 (s, 4H), 1.41 (d, J=5.0 Hz,2H).The result shows the solid is glycollate Form A.The XRPD data of the glycollate Form A is listed in Table11. The XRPD pattern is displayed in FIG. 19, the DSCcurve is displayed in FIG. 20, the TGA curve is displayed inFIG. 21

Reference： [1]Patent: US2017/342075,2017,A1 .Location in patent: Paragraph 0164; 0165; 0166; 0167; 0168; 0169

38
[ 19432-30-5 ]
[ 1211441-98-3 ]

Reference： [1]Patent: US2018/93950,2018,A1

39
C₈H₉N₃O₂ [ No CAS ]
[ 1211441-98-3 ]

Reference： [1]Patent: US2018/93950,2018,A1

40
[ 909767-89-1 ]
N-cyclopentyl-2-methoxy-5-(N,N-dimethylformamido)-3-pyrrylformonitrile [ No CAS ]
[ 1211441-98-3 ]

Yield	Reaction Conditions	Operation in experiment
70.3%	In 5,5-dimethyl-1,3-cyclohexadiene; at 120℃;Inert atmosphere;	In a nitrogen atmosphere, N-cyclopentyl-2-methoxy-5-(N,N-dimethyl-formamido)-3-pyrrylformonitrile (II) (2.6 g, 10 mmol), N-[5-(1-piperazino)-2-piperidyl] guanidine (III) (4.4 g, 20 mmol) and dimethylbenzene 15 mL were added in a reaction bottle, were heated to 120 C., and were subjected to stirring reaction for 20-24 hours to finish TLC detection reaction. A solvent was distilled off under reduced pressure, and was cooled to room temperature, methanol was added, and solid was separated out. The solid was filtered, a filter cake was washed twice with cold methanol, and was dried under vacuum to obtain off-white solid ribociclib (I) 3.05 g, and the yield was 70.3%; and EI-MS m/z: 435 [M+H]+, 1H NMR (DMSO-d6) delta1.63 (m, 2H), 1.99 (m, 4H), 2.50 (m, 2H), 3.05 (m, 10H), 3.28 (m, 4H), 4.62 (m, 1H), 6.24 (s, 1H), 7.47 (m, 1H), 8.03 (m, 1H), 8.21 (m, 1H), 8.78 (s, 1H) and 9.42 (s, 1H).

Reference： [1]Patent: US2018/93950,2018,A1 .Location in patent: Paragraph 0018; 0028

41
[ 3946-32-5 ]
[ 1211441-98-3 ]
7-cyclopentyl-2-( (5-(4-(8-(hydroxyamino)-8-oxooctanoyl)piperazin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2018,vol. 61,p. 3166 - 3192

42
[ 107-36-8 ]
[ 1211441-98-3 ]
ribociclib isethionic acid salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.9 g		Ribociclib (1.0 g) was dissolved in isopropanol (30 mL) and heated to 80 C and stirred for 10 minutes at the same temperature. A solution of isethionic acid (0.304 g) dissolved in isopropanol (5 mL) was added to the above solution at 80 C. The reaction mass was stirred at 80 C for 30 minutes. The reaction mass was cooled to 25 C to 35 C and stirred for 16 hours. The precipitated solid was filtered and washed with -hexane (2 x 5 mL). The wet solid was dried in hot air oven at 50 C for 16 hours to provide the title compound. (0172) Yield: 0 9 g; Purity by HPLC: 99 36 %

Reference： [1]Patent: WO2018/51280,2018,A1 .Location in patent: Page/Page column 21

43
[ 1211441-98-3 ]
[ 144-62-7 ]
7-cyclopentyl-N,N-dimethyl-2-[5-(piperazin-1-yl)pyridin-2-yl]amino}-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide hydrochloride oxalate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
79.5%	In isopropyl alcohol; at 0 - 60℃;Inert atmosphere;	Under inert atmosphere, Ribociclib base (5.0 g) was suspended in i-PrOH (125 mL), then oxalic acid (5.5 g) was added at 20 C. The suspension was heated to 60 C and a cloudy solution was obtained. The mixture was filtrated on a dicalite pad. The solution was cooled down to 0 C in 1 h, then kept under stirring at 0 C for 1.5 h. Ribociclib oxalate was isolated by filtration, washed with i-PrOH (10 mL) and dried under vacuum at 20 C for 2 days and at 50 C for 6 h. Ribociclib oxalate was obtained as a solid (4.8 g, 79.5% yield).
1 g		Ribociclib (1.0 g) was dissolved in isopropanol (30 mL) and heated to 80 C and stirred for 10 minutes at the same temperature. A solution of oxalic acid (0.217 g) dissolved in isopropanol (5 mL) was added to the above solution at 80 C. The reaction mass was stirred at 80 C for 30 minutes. The reaction mass was cooled to 25 C to 35 C and stirred for 16 hours. The precipitated solid was filtered and washed with -hexane (2 x 5 mL). The wet solid was dried in hot air oven at 50 C for 16 hours to provide the title compound. (0174) Yield: 1 0 g; Purity by HPLC: 98.37 %

Reference： [1]Patent: WO2019/40567,2019,A1 .Location in patent: Page/Page column 24
[2]Patent: WO2018/51280,2018,A1 .Location in patent: Page/Page column 22

44
[ 1211441-98-3 ]
[ 87-69-4 ]
ribociclib tartaric acid salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1.5 g		Ribociclib (1.5 g) was dissolved in isopropanol (45 mL) and heated to 80 C and stirred for 10 minutes at the same temperature. A solution of tartaric acid (0.544 g) dissolved in isopropanol (7.5 mL) was added to the above solution at 80 C. The reaction mass was stirred at 80 C for 30 minutes. The reaction mass was cooled to 25 C to 35 C and stirred for 16 hours. The precipitated solid was filtered and washed with -hexane (2 chi 7.5 mL). The wet solid was dried in hot air oven at 50 C for 16 hours to provide the title compound. (0177) Yield: 1.5 g; Purity by HPLC: 99.40 %

Reference： [1]Patent: WO2018/51280,2018,A1 .Location in patent: Page/Page column 22

45
[ 1211441-98-3 ]
[ 64-19-7 ]
7-cyclopentyl-N,N-dimethyl-2-[5-(piperazin-1-yl)pyridin-2-yl]amino}-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93.2%	In water; acetone; at 0 - 20℃; for 3.16667h;Inert atmosphere;	Under inert atmosphere, Ribociclib base (4.0 g) was suspended in water (12 mL), then acetic acid (1.1 mL) was added at 20 C. The suspension was kept under stirring for 30 min achieving complete dissolution. Acetone (80 mL) was added dropwise in 10 min to the ribociclib solution. The mixture was cooled down to 0 C in 1 h, then kept under stirring at 0 C for 1.5 h. Ribociclib acetate was isolated by filtration, washed with acetone (12 mL) and dried under vacuum at 50 C for 16 h. Ribociclib acetate was obtained as a white solid (93.2% yield).
0.8 g		Ribociclib (1.5 g) was dissolved in isopropanol (45 mL) and heated to 80 C and stirred for 10 minutes at the same temperature. A solution of acetic acid (0.217 g) dissolved in isopropanol (7.5 mL) was added to the above solution at 80 C. The reaction mass was stirred at 80 C for 30 minutes. The reaction mass was cooled to 25 C to 35 C and stirred for 16 hours. The precipitated solid was filtered and washed with -hexane (2 chi 7.5 mL). The wet solid was dried in hot air oven at 50 C for 16 hours to provide the title compound. (0183) Yield: 0 8 g; Purity by HPLC: 99 05 %

Reference： [1]Patent: WO2019/40567,2019,A1 .Location in patent: Page/Page column 24
[2]Patent: WO2018/51280,2018,A1 .Location in patent: Page/Page column 22

46
[ 1211441-98-3 ]
[ 76-05-1 ]
ribociclib trifluoroacetic acid salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1.3 g		Ribociclib (1.5 g) was dissolved in isopropanol (45 mL) and heated to 80 C and stirred for 10 minutes at the same temperature. A solution of trifluoroacetic acid (0.413 g) dissolved in isopropanol (7.5 mL) was added to the above solution at 80 C. The reaction mass was stirred at 80 C for 30 minutes. The reaction mass was cooled to 25 C to 35 C and stirred for 16 hours. The precipitated solid was filtered and washed with -hexane (2 chi 7.5 mL). The wet solid was dried in hot air oven at 50 C for 16 hours to provide the title compound. (0188) Yield: 1 3 g; Purity by HPLC: 99 66 %

Reference： [1]Patent: WO2018/51280,2018,A1 .Location in patent: Page/Page column 23

47
[ 1211441-98-3 ]
7-cyclopentyl-N,N-dimethyl-2-[5-(piperazin-1-yl)pyridin-2-yl]amino}-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide hydrochloride phosphate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95.1%	With phosphoric acid; In water; acetone; at 0 - 45℃; for 2.41667h;Inert atmosphere;	Under inert atmosphere, a solution of phosphoric acid (1.6 g) in water (9 mL) was added at 20 C to ribociclib base (3.0 g). The suspension was kept under stirring for 15 min at 20 C. No complete dissolution was achieved. The suspension was heated to 45 C and water (3.0 mL) was added. A cloudy solution was observed, to which acetone (60 mL) was added dropwise in 10 min. The suspension was cooled down to 0 C in 1 h, then kept under stirring at 0 C for 1 h. Ribociclib phosphate was isolated by filtration, washed with acetone (6 mL) and dried under vacuum at 50 C for 18 h. Ribociclib phosphate was obtained as a solid (3.5 g, 95.1% yield).
0.8 g		Ribociclib (1.5 g) was dissolved in isopropanol (45 mL) and heated to 80 C and stirred for 10 minutes at the same temperature. A solution of phosphoric acid (0.35 g) dissolved in isopropanol (7.5 mL) was added to the above solution at 80 C. The reaction mass was stirred at 80 C for 30 minutes. The reaction mass was cooled to 25 C to 35 C and stirred for 16 hours. The precipitated solid was filtered and washed with -hexane (2 chi 7.5 mL). The wet solid was dried in hot air oven at 50 C for 16 hours to provide the title compound. (0180) Yield: 0 8 g; Purity by HPLC: 99 25 %

Reference： [1]Patent: WO2019/40567,2019,A1 .Location in patent: Page/Page column 25
[2]Patent: WO2018/51280,2018,A1 .Location in patent: Page/Page column 22

48
[ 1211441-98-3 ]
ribociclib hydrobromic acid salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.8 g		Ribociclib (1.5 g) was dissolved in isopropanol (45 mL) and heated to 80 C and stirred for 10 minutes at the same temperature. An aqueous solution of hydrobromic acid (0.45 mL, 47 %) dissolved in isopropanol (7.5 mL) was added to the above solution at 80 C. The reaction mass was stirred at 80 C for 30 minutes. The reaction mass was cooled to 25 C to 35 C and stirred for 16 hours. The precipitated solid was filtered and washed with -hexane (2 chi 7.5 mL). The wet solid was dried in hot air oven at 50 C for 16 hours to provide the title compound. (0185) Yield: 0 8 g; Purity by HPLC: 99 38 %

Reference： [1]Patent: WO2018/51280,2018,A1 .Location in patent: Page/Page column 23

49
[ 1211441-98-3 ]
7-cyclopentyl-N,N-dimethyl-2-[5-(piperazin-1-yl)pyridin-2-yl]amino}-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide hydrochloride sulfate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	With sulfuric acid; In water; acetone; at 20℃; for 3.16667h;Inert atmosphere;	Under inert atmosphere, a solution of sulfuric acid (1.4 g) in water (9 mL) was added at 20 C to ribociclib base (3.0 g). The suspension was kept under stirring for 1.5 h at 20 C achieving complete dissolution. Acetone (60 mL) was added dropwise in 10 min to the Ribociclib solution. The resulting suspension was kept under stirring at 20 C for 1.5 h. Ribociclib sulfate was isolated by filtration, washed with acetone (6 mL) and dried under vacuum at 50 C for 18 h. Ribociclib sulfate was obtained as a solid (3.8 g, 100% yield).
1.72 g		Ribociclib (1.5 g) was dissolved in isopropanol (45 mL) and heated to 80 C and stirred for 10 minutes at the same temperature. A solution of sulfuric acid (0.355 g) dissolved in isopropanol (7.5 mL) was added to the above solution at 80 C. The reaction mass was stirred at 80 C for 30 minutes. The reaction mass was cooled to 25 C to 35 C and stirred for 16 hours. The precipitated solid was filtered and washed with -hexane (2 chi 7.5 mL). The wet solid was dried in hot air oven at 50 C for 16 hours to provide the title compound. (0194) Yield: 1 72 g; Purity by HPLC: 99 38 %

Reference： [1]Patent: WO2019/40567,2019,A1 .Location in patent: Page/Page column 25
[2]Patent: WO2018/51280,2018,A1 .Location in patent: Page/Page column 23

50
[ 1211441-98-3 ]
[ 77-92-9 ]
ribociclib citric acid salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1.7 g		Ribociclib (1.5 g) was dissolved in isopropanol (45 mL) and heated to 80 C and stirred for 10 minutes at the same temperature. A solution of citric acid (0.696 g) dissolved in isopropanol (7.5 mL) was added to the above solution at 80 C. The reaction mass was stirred at 80 C for 30 minutes. The reaction mass was cooled to 25 C to 35 C and stirred for 16 hours. The precipitated solid was filtered and washed with -hexane (2 chi 7.5 mL). The wet solid was dried in hot air oven at 50 C for 16 hours to provide the title compound. (0191) Yield: 1 7 g; Purity by HPLC: 98 65 %

Reference： [1]Patent: WO2018/51280,2018,A1 .Location in patent: Page/Page column 23

51
[ 1211441-98-3 ]
[ 104-15-4 ]
7-cyclopentyl-N,N-dimethyl-2-[5-(piperazin-1-yl)pyridin-2-yl]amino}-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide hydrochloride tosylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	In water; acetone; at 0 - 20℃; for 3.66667h;Inert atmosphere;	Under inert atmosphere, a solution of p-toluene sulfonic acid monohydrate (2.7 g) in water (9 mL) was added to ribociclib base (3.0 g) at 20 C. The suspension was kept under stirring for 1 h at 20 C achieving complete dissolution. Acetone (60 mL) was added dropwise in 10 min to the Ribociclib solution. The mixture was cooled down to 0 C in 1 h, no solid formation was observed. Upon addition of acetone (60 mL), a suspension was obtained, which was then kept under stirring at 0 C for 1.5 h. Ribociclib tosylate was isolated by filtration, washed with acetone (6 mL) and dried under vacuum for 18 h. Ribociclib Tosylate was obtained as a solid (4.3 g, 100% yield).
0.9 g		Ribociclib (1.5 g) was dissolved in isopropanol (45 mL) and heated to 80 C and stirred for 10 minutes at the same temperature. A solution of ^-toluenesulfonic acid (0.689 g) dissolved in isopropanol (7.5 mL) was added to the above solution at 80 C. The reaction mass was stirred at 80 C for 30 minutes. The reaction mass was cooled to 25 C to 35 C and stirred for 16 hours. The precipitated solid was filtered and washed with -hexane (2 chi 7.5 mL). The wet solid was dried in hot air oven at 50 C for 16 hours to provide the title compound. (0196) Yield: 0 9 g; Purity by HPLC: 99 65 %

Reference： [1]Patent: WO2019/40567,2019,A1 .Location in patent: Page/Page column 24-25
[2]Patent: WO2018/51280,2018,A1 .Location in patent: Page/Page column 24

52
tert-butyl 4-(6-((7-cyclopentyl-6-(hydroxymethyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperazine-1-carboxylate [ No CAS ]
[ 1211441-98-3 ]

Reference： [1]Patent: WO2018/51280,2018,A1

53
2-chloro-4-cyclopentylamino-5-(propynyl)pyrimidine [ No CAS ]
[ 1211441-98-3 ]

Reference： [1]Patent: CN107936029,2018,A

54
[ 1178566-48-7 ]
[ 1211441-98-3 ]

Reference： [1]Patent: CN107936029,2018,A

55
[ 1211441-98-3 ]
6-(((S)-1-((2S,4R)-4-hydroxy-2-((4-(4-methylthiazol-5-yl)benzyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)amino)-6-oxohexanoic acid [ No CAS ]
7-cyclopentyl-2-((5-(4-(6-(((S)-1-((2S,4R)-4-hydroxy-2-((4-(4-methylthiazol-5-yl)benzyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)amino)-6-oxohexanoyl)piperazin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84%	With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; triethylamine; In dichloromethane; N,N-dimethyl-formamide; at 20℃; for 1h;	To a solution of ribociclib0.021 mmol) and linker 3 (14 mg, 0.025 mmol) in DCM/DMF (1:1, 2 ml) were added triethylamine (17 iil, 0.12 mmol) and TBTU (8 mg, 0.025 mmol). The reaction was stirred at RT for 1 h before being concentrated under reduced pressure. The resulting residue was dissolved in MeOH, and purified by prep-HPLC to yield the product (19 mg, 84%) as yellow solid. ?H NMR (600 MHz, CD3OD) of major isomer (rotamer ratio 6:1) oe 9.02 (s, 1H), 8.97 (s,1H), 8.08 (dd, J= 9.6, 2.4 Hz, 1H), 7.87 (d, J= 2.4 Hz, 1H), 7.48 (d, J 7.8 Hz, 2H), 7.45 (d,J= 10.2 Hz, 1H), 7.43 (d, J= 8.4 Hz, 1H), 6.82 (s, 1H), 4.86-4.80 (m, 1H), 4.65 (s, 1H), 4.62-4.52 (m, 3H), 4.38 (d, J 16.8 Hz, 1H), 3.93 (d, J= 10.8 Hz, 1H), 3.84-3.76 (m, 5H), 3.29 (t,J 4.8 Hz, 2H), 3.24 (t, J 4.8 Hz, 2H), 3.19 (s, 3H), 3.17 (s, 3H), 2.52-2.47 (m, 7H), 2.39-2.30 (m, 3H), 2.14-2.08 (m, 5H), 1.77-1.64 (m, 6H), 1.06 (s, 9H); HRMS(ESI-TOF) m/z:[M+Hj calculated for C51H67N1206S, 975.5022, found 975.5024.

Reference： [1]Patent: WO2018/106870,2018,A1 .Location in patent: Page/Page column 85; 106; 107

56
[ 927670-97-1 ]
[ 1211441-98-3 ]
7-cyclopentyl-2-((5-(4-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)glycyl)piperazin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
74%	With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; triethylamine; In dichloromethane; at 20℃; for 1h;Darkness;	To a solution of ribociclib (12 mg, 0.027 mmol) and mmol) and TBTU (12 mg, 0.03 8 mmol). The reaction solution was stirred at RT for 1 h before being concentrated under reduced pressure. The resulting residue was dissolved in MeOH andpurified by prep-HPLC to yield the desired product (15 mg, 74%) as yellow solid. ?H NMR (CD3OD, 600 MHz) oe 8.86 (s, 1H), 7.89 (dd, J 8.4, 2.4 Hz, 1H), 7.82 (d, J= 2.4 Hz, 1H),7.52-7.49 (m, 2H), 7.08 (d, J= 7.2 Hz, 1H), 6.90 (d, J= 8.4 Hz, 1H), 6.65 (s, 1H), 4.96-4.93(m, 1H), 4.78-4.72 (m, 1H), 4.17 (s, 2H), 3.85-3.83 (m, 2H), 3.72-3.72 (m, 2H), 3.30-3.28 (m,2H), 3.23-3.21 (m, 2H), 3.18 (s, 3H), 3.15 (s, 3H), 2.84-2.73 (m, 3H), 2.46-2.40 (m, 2H), 2.15-2.02 (m, 5H), 1.75-1.67 (m, 2H). HRMS(ESI-TOF) m/z: [M+Hj calculated for C38H41N1106,748.3314, found 748.3391.

Reference： [1]Patent: WO2018/106870,2018,A1 .Location in patent: Page/Page column 85; 110; 111

57
C₁₅H₁₉N₃O₂S [ No CAS ]
[ 1211441-98-3 ]

Reference： [1]Patent: CN108623599,2018,A

58
5-iodo-2-chloro-4-(cyclopentylamino)pyrimidine [ No CAS ]
[ 1211441-98-3 ]

Reference： [1]Patent: CN108586356,2018,A
[2]Patent: CN108586356,2018,A
[3]Patent: CN108586356,2018,A

59
methyl 2-chloro-4-cyclopentylaminopyrimidine-5-carboxylate [ No CAS ]
[ 1211441-98-3 ]

Reference： [1]Patent: CN108586356,2018,A
[2]Patent: CN108586356,2018,A
[3]Patent: CN108586356,2018,A

60
2-((2-chloro-5-formylpyrimidin-4-yl)(cyclopentylamino))-N,N-dimethylacetamide [ No CAS ]
[ 1211441-98-3 ]

Reference： [1]Patent: CN108586356,2018,A

61
ethyl 2-((2-chloro-5-formylpyrimidin-4-yl)(cyclopentylamino))acetate [ No CAS ]
[ 1211441-98-3 ]

Reference： [1]Patent: CN108586356,2018,A
[2]Patent: CN108586356,2018,A

62
methyl 2-chloro-4-(cyclopentyl(2-(dimethylamino)-2-oxoethyl)amino)pyrimidine-5-carboxylate [ No CAS ]
[ 1211441-98-3 ]

Reference： [1]Patent: CN108586356,2018,A

63
methyl 2-chloro-4-(cyclopentyl(2-ethoxy-2-oxoethyl)amino)pyrimidine-5-carboxylate [ No CAS ]
[ 1211441-98-3 ]

Reference： [1]Patent: CN108586356,2018,A
[2]Patent: CN108586356,2018,A

64
[ 871254-61-4 ]
[ 1211441-98-3 ]

Reference： [1]Patent: CN108586356,2018,A
[2]Patent: CN108586356,2018,A
[3]Patent: CN108586356,2018,A

65
N,N-dimethyl(2-cyclopentylamino)acetamide [ No CAS ]
[ 1211441-98-3 ]

Reference： [1]Patent: CN108586356,2018,A
[2]Patent: CN108586356,2018,A

66
ethyl 2-chloro-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylate [ No CAS ]
[ 1211441-98-3 ]

Reference： [1]Patent: CN108586356,2018,A
[2]Patent: CN108586356,2018,A

67
[ 1211443-58-1 ]
[ 1211441-98-3 ]

Reference： [1]Patent: CN108586356,2018,A
[2]Patent: WO2019/142206,2019,A1

68
2-chloro-7-cyclopentyl-N,N-dimethyl-5-oxo-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine-6-carboxamide [ No CAS ]
[ 1211441-98-3 ]

Reference： [1]Patent: CN108586356,2018,A

69
ethyl 2-chloro-7-cyclopentyl-5-oxo-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine-6-carboxylate [ No CAS ]
[ 1211441-98-3 ]

Reference： [1]Patent: CN108586356,2018,A
[2]Patent: CN108586356,2018,A

70
2-chloro-7-cyclopentyl-5-hydroxy-N,N-dimethyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine-6-carboxamide [ No CAS ]
[ 1211441-98-3 ]

Reference： [1]Patent: CN108586356,2018,A

71
ethyl 2-chloro-7-cyclopentyl-5-hydroxy-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine-6-carboxylate [ No CAS ]
[ 1211441-98-3 ]

Reference： [1]Patent: CN108586356,2018,A
[2]Patent: CN108586356,2018,A

72
ethyl 2-((5-(4-(tert-butoxycarbonyl)piperazin-1-yl)pyridin-2-yl)amino)-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylate [ No CAS ]
[ 1211441-98-3 ]

Reference： [1]Patent: CN108586356,2018,A

73
2-((5-(4-(tert-butoxycarbonyl)piperazin-1-yl)pyridin-2-yl)amino)-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-formic acid [ No CAS ]
[ 1211441-98-3 ]

Reference： [1]Patent: CN108586356,2018,A

74
[ 3177-20-6 ]
[ 1211441-98-3 ]

Reference： [1]Patent: CN108586356,2018,A
[2]Patent: CN108586356,2018,A
[3]Patent: CN108586356,2018,A

75
2-chloro-4-cyclopentylaminopyrimidine-5-aldehyde [ No CAS ]
[ 1211441-98-3 ]

Reference： [1]Patent: CN108586356,2018,A
[2]Patent: CN108586356,2018,A
[3]Patent: CN108586356,2018,A

76
[ 1211441-98-3 ]
[ 1211443-80-9 ]

Yield	Reaction Conditions	Operation in experiment
100%	With hydrogenchloride; In methanol; at 20℃; for 2h;	Ribociclib (100.0 mg, 0.23 mmol) was dissolved in 50 mL of a 14 methanol solution of 83 hydrogen chloride (4.0 mol/L), and the resulting mixture was stirred at room temperature for 2 h and concentrated to obtain ribociclib 98 hydrochloride (108.4 mg, yield: 100.0%). 1H NMR (400 MHz, DMSO-d6): 11.68 (1H, s), 9.68 (2H, s), 9.04 (1H, s), 8.12 (1H, dd, J=9.2 Hz, 2.8 Hz), 7.99 (1H, d, J = 2.8 Hz), 7.65 (1H, d, J=9.2 Hz), 6.85 (1H, s), 4.77-4.86 (1H, m), 3.44-3.47 (4H, m), 3.21-3.30 (4H, m), 3.06 (3H, s), 2.51 (3H, s), 2.27-2.42 (2H, m), 1.93-2.09 (4H, m), 1.58-1.72 (2H, m)

Reference： [1]Patent: EP3434676,2019,A1 .Location in patent: Paragraph 0141; 0142

77
[ 1211441-98-3 ]
7-cyclopentyl-N,N-dimethyl-2-[5-(piperazin-1-yl)pyridin-2-yl]amino}-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95.5%	With hydrogenchloride; In water; acetone; at 0 - 20℃; for 3.66667h;Inert atmosphere;	Under inert atmosphere, Ribociclib base (4.0 g) was suspended in water (12 mL), then aq. hydrochloric acid 37% (1.8 mL) was added at 20 C. The suspension was kept under stirring for 20 min achieving complete dissolution. Acetone (80 mL) was added dropwise in 20 min to the Ribociclib solution. The mixture was cooled down to 0 C in 1 h, then kept under stirring at 0 C for 2 h. Ribociclib hydrochloride was isolated by filtration, washed with acetone (12 mL) and dried under vacuum at 50 C for 16 h. Ribociclib hydrochloride was obtained as a yellow solid (95.5% yield).

Reference： [1]Patent: WO2019/40567,2019,A1 .Location in patent: Page/Page column 23-24

78
[ 617-48-1 ]
[ 1211441-98-3 ]
7-cyclopentyl-N,N-dimethyl-2-[5-(piperazin-1-yl)pyridin-2-yl]amino}-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide hydrochloride malate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78.9%	In water; acetone; at -5 - 20℃; for 3.25h;Inert atmosphere;	Under inert atmosphere, a solution of DL-malic acid (1.9 g) in water (9 mL) was added at 20 C to ribociclib base (3.0 g). The suspension was kept under stirring for 20 min at 20 C, achieving complete dissolution. Acetone (60 mL) was added dropwise in 10 min to the Ribociclib solution. The suspension was kept under stirring at 20 C for 1 h, then cooled down to -5 C in 45 min and kept under stirring at -5 C for 1 h. Ribociclib malate was isolated by filtration, washed with acetone (6 mL) and dried under vacuum for 72 h. Ribociclib malate was obtained as a solid (3.1 g, 78.9% yield).

Reference： [1]Patent: WO2019/40567,2019,A1 .Location in patent: Page/Page column 25-26

79
[ 1211441-98-3 ]
[ 110-16-7 ]
7-cyclopentyl-N,N-dimethyl-2-[5-(piperazin-1-yl)pyridin-2-yl]amino}-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide hydrochloride maleate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
34%	In water; acetone; at -5 - 45℃; for 2.16667h;Inert atmosphere;	Under inert atmosphere, a solution of maleic acid (1.6 g) in water (9 mL) was added at 20 C to ribociclib base (3.0 g). The suspension was kept under stirring for 15 min at 20 C, achieving complete dissolution. Acetone (60 mL) was added dropwise in 10 min to the Ribociclib solution. The mixture was cooled down to -5 C in 45 min. The resulting suspension was diluted with further acetone (30 mL), then kept under stirring at -5 C for 1 h. Ribociclib maleate was isolated by filtration, washed with acetone (6 mL) and dried under vacuum at 50 C for 18 h. Ribociclib maleate was obtained as a solid (1.3 g, 34.0% yield).

Reference： [1]Patent: WO2019/40567,2019,A1 .Location in patent: Page/Page column 26

80
[ 75-75-2 ]
[ 1211441-98-3 ]
7-cyclopentyl-N,N-dimethyl-2-[5-(piperazin-1-yl)pyridin-2-yl]amino}-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide hydrochloride mesylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
91.2%	In water; acetone; at -5 - 20℃; for 3.58333h;Inert atmosphere;	Under inert atmosphere, Ribociclib base (4.0 g) was suspended in water (12 mL), then methane sulfonic acid (1.2 mL) was added at 20 C. The suspension was kept under stirring for 20 min achieving complete dissolution. Acetone (60 mL) was added dropwise in 15 min to the ribociclib solution. The mixture was cooled down to -5 C in 1 h. No solid formation was observed. Additional acetone (100 mL) was added, causing product precipitation. The suspension was kept under stirring at -5 C for 2 h. Ribociclib mesylate was isolated by filtration, washed with acetone (12 mL) and dried under vacuum at 50 C for 16 h. Ribociclib mesylate was obtained as a solid (91.2% yield).

Reference： [1]Patent: WO2019/40567,2019,A1 .Location in patent: Page/Page column 24

81
4-(6-[7-cyclopentyl-6-(dimethylcarbamoyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl]amino}pyridin-3-yl)piperazin-1-ium trifluoroacetate [ No CAS ]
[ 1211441-98-3 ]

Yield	Reaction Conditions	Operation in experiment
93%	With sodium hydroxide; In water;pH 11 - 12;	Method-1 To a solution of 4-(6-[7-cyclopentyl-6-(dimethylcarbamoyl)-7H-pyrrolo[2,3-d] pyrimidin-2-yl]amino } pyridin-3 -yl)piperazin- 1 -ium trifluoroacetate (100 g) in 2500 ml of distilled water was added 20% sodium hydroxide solution and adjusted to a pH ii-i2. The reaction was stirred for over 5-6 hrs. The solid wascollected by filtration followed by drying at 45-55C to give an off white to tan solid (76 g).Yield: 93.0 %; HPLC Purity: 99.8%

Reference： [1]Patent: WO2019/82143,2019,A1 .Location in patent: Page/Page column 42

82
[ 1211441-98-3 ]
tert-butyl N-(2-(2-(2-(2-bromoethoxy)ethoxy)ethoxy)ethyl)carbamate [ No CAS ]
C₃₄H₅₁N₉O₅ [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2019,vol. 58,p. 6321 - 6326
Angew. Chem.,2019,vol. 131,p. 6387 - 6392,6

83
[ 1211441-98-3 ]
C₂₇H₃₉N₉O [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2019,vol. 58,p. 6321 - 6326
Angew. Chem.,2019,vol. 131,p. 6387 - 6392,6

84
[ 1211441-98-3 ]
7-cyclopentyl-2-((5-(4-(4-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetamido)butyl)piperazin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2019,vol. 58,p. 6321 - 6326
Angew. Chem.,2019,vol. 131,p. 6387 - 6392,6

85
[ 1211441-98-3 ]
7-cyclopentyl-2-((5-(4-(2-(2-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethoxy)ethoxy)ethyl)piperazin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2019,vol. 58,p. 6321 - 6326
Angew. Chem.,2019,vol. 131,p. 6387 - 6392,6

86
[ 1211441-98-3 ]
C₂₉H₄₃N₉O₃ [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2019,vol. 58,p. 6321 - 6326
Angew. Chem.,2019,vol. 131,p. 6387 - 6392,6

87
[ 1211441-98-3 ]
7-cyclopentyl-2-((5-(4-(4-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)butyl)piperazin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2019,vol. 58,p. 6321 - 6326
Angew. Chem.,2019,vol. 131,p. 6387 - 6392,6

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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CAS No. :	1211441-98-3	MDL No. :	MFCD27976795
Formula :	C₂₃H₃₀N₈O	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	RHXHGRAEPCAFML-UHFFFAOYSA-N
M.W :	434.54	Pubchem ID :	44631912
Synonyms :	LEE011

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P280-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302	Packing Group:	N/A
GHS Pictogram:

Precautionary Statements-General
Code	Phrase
P101	If medical advice is needed,have product container or label at hand.
P102	Keep out of reach of children.
P103	Read label before use
Prevention
Code	Phrase
P201	Obtain special instructions before use.
P202	Do not handle until all safety precautions have been read and understood.
P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
P211	Do not spray on an open flame or other ignition source.
P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
P232	Protect from moisture.
P233	Keep container tightly closed.
P234	Keep only in original container.
P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
P243	Take precautionary measures against static discharge.
P244	Keep reduction valves free from grease and oil.
P250	Do not subject to grinding/shock/friction.
P251	Pressurized container: Do not pierce or burn, even after use.
P260	Do not breathe dust/fume/gas/mist/vapours/spray.
P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

Physical hazards
Code	Phrase
H200	Unstable explosive
H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
H203	Explosive; fire, blast or projection hazard
H204	Fire or projection hazard
H205	May mass explode in fire
H220	Extremely flammable gas
H221	Flammable gas
H222	Extremely flammable aerosol
H223	Flammable aerosol
H224	Extremely flammable liquid and vapour
H225	Highly flammable liquid and vapour
H226	Flammable liquid and vapour
H227	Combustible liquid
H228	Flammable solid
H229	Pressurized container: may burst if heated
H230	May react explosively even in the absence of air
H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
H290	May be corrosive to metals
Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed
H304	May be fatal if swallowed and enters airways
H305	May be harmful if swallowed and enters airways
H310	Fatal in contact with skin
H311	Toxic in contact with skin
H312	Harmful in contact with skin
H313	May be harmful in contact with skin
H314	Causes severe skin burns and eye damage
H315	Causes skin irritation
H316	Causes mild skin irritation
H317	May cause an allergic skin reaction
H318	Causes serious eye damage
H319	Causes serious eye irritation
H320	Causes eye irritation
H330	Fatal if inhaled
H331	Toxic if inhaled
H332	Harmful if inhaled
H333	May be harmful if inhaled
H334	May cause allergy or asthma symptoms or breathing difficulties if inhaled
H335	May cause respiratory irritation
H336	May cause drowsiness or dizziness
H340	May cause genetic defects
H341	Suspected of causing genetic defects
H350	May cause cancer
H351	Suspected of causing cancer
H360	May damage fertility or the unborn child
H361	Suspected of damaging fertility or the unborn child
H361d	Suspected of damaging the unborn child
H362	May cause harm to breast-fed children
H370	Causes damage to organs
H371	May cause damage to organs
H372	Causes damage to organs through prolonged or repeated exposure
H373	May cause damage to organs through prolonged or repeated exposure
Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere

[ CAS No. 1211441-98-3 ] {[proInfo.proName]}

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[ 1211441-98-3 ] Synthesis Path-Downstream 1~87

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[ CAS No. 1211441-98-3 ] {[proInfo.proName]}

Quality Control of [ 1211441-98-3 ]

Related Doc. of [ 1211441-98-3 ]

Product Details of [ 1211441-98-3 ]

Safety of [ 1211441-98-3 ]

Application In Synthesis of [ 1211441-98-3 ]

[ 1211441-98-3 ] Synthesis Path-Downstream 1~87

Similar Product of [ 1211441-98-3 ]

Precautionary Statements-General

Prevention

Response

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Environmental hazards

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Similar Product of
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