Name: 684-07-1|3,3,3-Trifluoro-2-hydroxypropanoic acid|98%
Brand: Ambeed
SKU: A525993
Rating: 97 (40 reviews)

1
[ 67-56-1 ]
[ 684-07-1 ]
[ 93496-85-6 ]

Yield	Reaction Conditions	Operation in experiment
71%	With sulfuric acid for 0.05h; Heating;
	With sulfuric acid

Reference： [1]Haydock; Mulholland; Telford; et al. [European Journal of Medicinal Chemistry, 1984, vol. 19, # 3, p. 205 - 214]
[2]Current Patent Assignee: AKZO NOBEL NV - FR2293196, 1976, B1 [Chem.Abstr., 1976, vol. 85, # 94079][Chem.Abstr., 1976, vol. 85, # 94079]

2
[ 111724-96-0 ]
[ 684-07-1 ]

Yield	Reaction Conditions	Operation in experiment
	With oxonium
	With sulfuric acid Heating;

Reference： [1]Kubota, T.; Shirakura, H.; Tanaka, T. [Journal of Fluorine Chemistry, 1991, vol. 54, # 1-3, p. 286]
[2]Kubota, Toshio; Iijima, Masahiro; Tanaka, Tatsuo [Tetrahedron Letters, 1992, vol. 33, # 10, p. 1351 - 1354]

3
[ 2216-51-5 ]
[ 684-07-1 ]
(R)-3,3,3-Trifluoro-2-hydroxy-propionic acid (1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester [ No CAS ]
(S)-3,3,3-Trifluoro-2-hydroxy-propionic acid (1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogen cation

Reference： [1]Kubota, T.; Shirakura, H.; Tanaka, T. [Journal of Fluorine Chemistry, 1991, vol. 54, # 1-3, p. 286]

4
[ 94726-00-8 ]
[ 684-07-1 ]

Yield	Reaction Conditions	Operation in experiment
80%	With hydrogenchloride for 4h; Heating;

Reference： [1]Bussche-Huennefeld, Christoph von .; Cescato, Claudio; Seebach, Dieter [Chemische Berichte, 1992, vol. 125, # 12, p. 2795 - 2802]

Yield	Reaction Conditions	Operation in experiment
	Trifluoracetaldehyd, KCN, H2SO4, W.;
	2H-Pentafluor-propen, Dinitrogenperoxid, 1,2,2-Trifluor-1,1,2-trichlor-aethan, 90 - 100grad, 1 h, neben anderen Prodd.; nicht rein erhalten; als Hydrat isoliert;
	aus d. Olefin durch Oxid. m. N2O4;

6
[ 13089-11-7 ]
[ 684-07-1 ]

Yield	Reaction Conditions	Operation in experiment
41%	Stage #1: methyl 3,3,3-trifluoropyruvate With isopropyl alcohol at 250℃; for 6h; Stage #2: With hydrogenchloride for 6h; Heating;

Reference： [1]Lermontov, Sergei A.; Shkavrov, Sergei V.; Kuryleva, Nina V. [Journal of Fluorine Chemistry, 2003, vol. 121, # 2, p. 223 - 225]

7
[ 13089-11-7 ]
[ 67-63-0 ]
[ 684-07-1 ]
[ 93496-85-6 ]
(R,S)-isopropyl 3,3,3-trifluoro-2-hydroxypropanoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	at 250℃; for 6h;

Reference： [1]Lermontov, Sergei A.; Shkavrov, Sergei V.; Kuryleva, Nina V. [Journal of Fluorine Chemistry, 2003, vol. 121, # 2, p. 223 - 225]

8
[ 126266-75-9 ]
[ 684-07-1 ]

Yield	Reaction Conditions	Operation in experiment
92%	With sodium hydroxide at 25℃; for 1h;
92%	Stage #1: 3,3-dichloro-1,1,1-trifluoroacetone With sodium hydroxide In water at 25℃; for 3.5h; Stage #2: With hydrogenchloride In water at 25℃;	1 EXAMPLE 1 The step (a) of the present invention was conducted as follows. At first, 235 g (1 mol, 1 eq.) of 1,1-dichloro-3,3,3-trifluoroacetone trihydrate were added dropwise by spending 2.5 hr to 533 g (4 mol, 4 eq.) of 30 wt % sodium hydroxide aqueous solution under cooling with ice, while the internal temperature of the reaction liquid was maintained at 25 C. or lower, followed by stirring for 1 hr. After that, 197 g (2 mol, 2 eq.) of 37 wt % hydrochloric acid aqueous solution were added dropwise to the reaction liquid under cooling with ice, while the internal temperature of the reaction liquid was maintained at 25 C. or lower. Then, 180 ml of water were added under room temperature to dissolve the precipitated sodium chloride. The resulting solution was extracted two times with 500 ml of ethyl acetate. Then, the combined organic layer was washed one time with 500 ml of saturated brine, concentrated and dried under vacuum, thereby obtaining 163 g of a crude product of 3,3,3-trifluoro-2-hydroxypropionic acid. This crude product was found by 1H-NMR to contain 81.5 wt % of 3,3,3-trifluoro-2-hydroxypropionic acid (yield: 92%). This crude product was used in the following step (b) of Example 2 without conducting a further purification. The obtained 3,3,3-trifluoro-2-hydroxypropionic acid was found to have the following characteristics. 1H-NMR (standard substance: TMS; solvent: CD3OD), δ ppm: 4.53 (q, 7.6 Hz, 1H); 19F-NMR (standard substance: C6F6, solvent: CD3OD), δ ppm: 87.75 (d, 7.6 Hz).
	Stage #1: 3,3-dichloro-1,1,1-trifluoroacetone With sodium hydroxide In water at 20 - 30℃; Stage #2: With hydrogenchloride In water

Alkaline conditions;

Reference： [1]Ishii, Akihiro; Kanai, Masatomi; Yasumoto, Manabu; Inomiya, Kenjin; Kuriyama, Yokusu; Katsuhara, Yutaka [Journal of Fluorine Chemistry, 2004, vol. 125, # 4, p. 567 - 571]
[2]Current Patent Assignee: CENTRAL GLASS CO LTD - US2004/49076, 2004, A1 Location in patent: Page 5
[3]Location in patent: experimental part Yasumoto, Manabu; Ueki, Hisanori; Ono, Taizo; Katagiri, Toshimasa; Soloshonok, Vadim A. [Journal of Fluorine Chemistry, 2010, vol. 131, # 4, p. 535 - 539]
[4]Wong, Lawrence W.-Y.; Vashchenko, Elena V.; Zhao, Ying; Sung, Herman H.-Y.; Vashchenko, Valerii V.; Mikhailenko, Vadim; Krivoshey, Alexander I.; Williams, Ian D. [Chirality, 2019, vol. 31, # 11, p. 979 - 991]

9
[ 5348-42-5 ]
[ 684-07-1 ]
[ 882978-54-3 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride for 18h; Heating;
	With hydrogenchloride In water at 108℃; for 18h;	90 4,5-Dichloro-benzene-1,2-diamine (8.50 g; 48.0 mmoles) and 3,3,3-trifIuoro-2-hydroxy-propionic acid (10.59 g; 73.52 mmoles) were suspended in 6N HCl (19 mL; 114 mmoles) under a nitrogen atmosphere. The reaction was stirred vigorously and heated to 108°C for 18 hrs, then cooled to room20 temperature. The reaction was diluted with water (200 mL) and with ethyl acetate (200 mL), then sodium bicarbonate (6.05 g; 72.0 mmoles) was added, slowly and in portions to quench the reaction. The aqueous layer was separated and extracted with ethyl acetate (3x80 mL). The extracts were combined, washed with water (60 mL) and brine (60 mL), then dried over Na2SO4. The filtrate was concentrated in vacuo to yield a crude brown solid which was then purified by column chromatography (SiO2; 30% ethyl acetate/CH2Cl2) to yield the title compound as a brown solid. 1H NMR (400 MHz, CD3CN) δ 7.80 (s, 2H), δ 5.43 (q, J = 6.8 Hz, 1 H) MS calculated for C9H5Cl2F3N2O: 283.97 MS measured: 285, 287 (M+H); 283, 285 (M-H).
	Stage #1: 4,5-Dichloro-1,2-phenylenediamine; 3,3,3-trifluoro-2-hydroxy-propionic acid With hydrogenchloride In water at 108℃; for 18h; Stage #2: With sodium hydrogencarbonate In water; ethyl acetate	90 4,5-Dichloro-benzene-1 ,2-diamine (8.50 g; 48.0 mmoles) and 3,3,3- trifluoro-2-hydroxy-propionic acid (10.59 g; 73.52 mmoles) were suspended in 6N HCI (19 mL; 114 mmoles) under a nitrogen atmosphere. The reaction was stirred vigorously and heated to 108°C for 18 hrs, then cooled to room temperature. The reaction was diluted with water (200 mL) and with ethyl acetate (200 mL), then sodium bicarbonate (6.05 g; 72.0 mmoles) was added slowly and in portions to quench the reaction. The aqueous layer was separated and extracted with ethyl acetate (3x80 mL). The extracts were combined, washed with water (60 mL) and brine (60 mL), then dried over Na2SO4. The filtrate was concentrated in vacuo to yield a crude brown solid which was then purified by column chromatography (SiO2; 30% ethyl acetate/CH2CI2) to yield the title compound as a brown solid. EPO 1H NMR (400 MHz, CD3CN) δ 7.80 (s, 2H), δ 5.43 (q, J = 6.8 Hz1 1 H)MS calculated for C9H5CI2F3N2O: 283.97MS measured: 285, 287 (M+H); 283, 285 (M-H).

Stage #1: 4,5-Dichloro-1,2-phenylenediamine; 3,3,3-trifluoro-2-hydroxy-propionic acid With hydrogenchloride In water at 100℃; for 18h; Heating / reflux; Stage #2: With sodium hydrogencarbonate In water; ethyl acetate

1 A 1-L 4-neck flask equipped with a thermocouple controller, an overhead mechanical stirrer, a condenser, and a nitrogen inlet/outlet adaptor was charged with 4,5-dichloro-1 ,2-phenylenediamine (71.3 g, 0.403 mol), trifluorolactic acid (87.0 g, 0.604 mol) and 4N HCI (340 ml_). The reaction mixture was heated for 18 h at reflux (100°C). The resulting solution was cooled to room temperature and then diluted with EtOAc (1 L) and H2O (1 L). The solution was slowly treated with NaHCO3 (500 g) until pH 8-9. After the effervescence ceased, the phases were split and aqueous layer was back extracted with EtOAc (3 x 1 L). The combine organic phase was washed with H2O (1 L) and brine (1 L); dried over MgSO4, filtered and evaporated to dryness to yield a crude residue. The crude residue was purified by flash chromatography using SiO2 (2 kg) and 10% EtOAc/CH2CI2 (2 L) and 20% EtOAc/CH2CI2 (32 L) and the product dried in vacuo for 18 h at 60 0C to yield the title compound as a brownish solid.

Reference： [1]Ng, Raymond A.; Lanter, James C.; Alford, Vernon C.; Allan, George F.; Sbriscia, Tifanie; Lundeen, Scott G.; Sui, Zhihua [Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 6, p. 1784 - 1787]
[2]Current Patent Assignee: JOHNSON & JOHNSON INC - WO2006/39243, 2006, A1 Location in patent: Page/Page column 105
[3]Current Patent Assignee: JOHNSON & JOHNSON INC - WO2006/39215, 2006, A2 Location in patent: Page/Page column 107-108
[4]Current Patent Assignee: JOHNSON & JOHNSON INC - WO2007/87518, 2007, A2 Location in patent: Page/Page column 35-36

10
[ 64-17-5 ]
[ 684-07-1 ]
[ 94726-00-8 ]

Yield	Reaction Conditions	Operation in experiment
68%	With sulfuric acid In ethanol for 42h; Heating / reflux;	2 EXAMPLE 2 The step (b) of the present invention was conducted as follows. At first, 2.84 g of the crude product obtained by Example 1 (containing 16.07 mmol (1.00 eq.) of 3,3,3-trifluoro-2-hydroxypropionic acid) and 19.6 mg (0.20 mmol, 0.01 eq.) of 98% sulfuric acid were added to 20 ml of ethanol, followed by stirring for 43 hr with heating under reflux. The resulting reaction liquid itself was subjected to a vacuum distillation (52 C./3,500 Pa), thereby obtaining 1.87 g of white, needle-like crystals of ethyl 3,3,3-trifluoro-2-hydroxypropionate of the following formula 8. The yield was 68%. The obtained crude product (the white, needle-like crystals) was used in the following step (c) of Example 3 without conducting a further purification. Ethyl 3,3,3-trifluoro-2-hydroxypropionate was found to have the following characteristics. 1H-NMR (standard substance: TMS; solvent: CDCl3), δ ppm: 1.35 (t, 7.6 Hz, 3H), 3.42 (br, 1H), 4.30-4.47 (m, 2H), 4.47 (q, 7.6 Hz, 1H); 19F-NMR (standard substance: C6F6, solvent: CDCl3), δ ppm: 85.58 (d, 7.6 Hz).

Reference： [1]Current Patent Assignee: CENTRAL GLASS CO LTD - US2004/49076, 2004, A1 Location in patent: Page 5

11
[ 684-07-1 ]
[ 139512-70-2 ]
1-(5-chloro-6-fluoro-1H-benzoimidazol-2-yl)-2,2,2-trifluoro-ethanol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; In water; at 108℃; for 18h;	4-Chloro-5-fluoro-benzene-1,2-diamine (5.20 g; 32.4 mmoles) and 3,3,3-trifluoro-2-hydroxy-propionic acid (7.00 g; 48.6 mmoles) were suspended in 6N HCl (9 mL; 54 mmoles) under a nitrogen atmosphere. The reaction was stirred vigorously and heated to 108C for 18 hrs, then cooled to room temperature. The reaction was diluted with water (100 mL) and with ethyl acetate (100 mL), then sodium bicarbonate (6.90 g; 81.00 mmoles) was added slowly and in portions to quench the reaction. The aqueous layer was separated and extracted with ethyl acetate (3x40 mL). The extracts were combined, washed with water (30 mL) and brine (30 mL), then dried over Na2SO4. The filtrate was concentrated in vacuo to yield a crude brown solid which was then purified by column chromatography (SiO2; 30% ethyl acetate/CH2Cl2) to yield the title compound as an off-white solid. 1H NMR (400 MHz, CD3CN) delta 7.74 (d, J = 6.7 Hz, 1 H), delta 7.49 (d, J =9.5,1 H), delta 5.41 (q, J = 6.8 Hz, 1 H), delta 5.16 (br s, 1 H), delta 2.35 (s, 6H) MS calculated for C9H5ClF4N2O: 268.00 MS measured: 269 (M+H); 267 (M-H).
		4-Chloro-5-fluoro-benzene-1 ,2-diamine (5.20 g; 32.4 mmoles) and 3,3,3- trifluoro-2-hydroxy-propionic acid (7.00 g; 48.6 mmoles) were suspended in 6N HCI (9 ml 54 mmoles) under a nitrogen atmosphere. The reaction was stirred vigorously and heated to 108C for 18 hrs, then cooled to room temperature. The reaction was diluted with water (100 ml_) and with ethyl acetate (100 ml_), then sodium bicarbonate (6.90 g; 81.00 mmoles) was added slowly and in portions to quench the reaction. The aqueous layer was separated and extracted with ethyl acetate (3x40 ml_). The extracts were combined, washed with water (30 ml_) and brine (30 mL), then dried over Na2SO4. The filtrate was concentrated in vacuo to yield a crude brown solid which was then purified by column chromatography (SiO2; 30% ethyl acetate/CH2CI2) to yield the title compound as an off-white solid.1H NMR (400 MHz, CD3CN) delta 7.74 (d, J = 6.7 Hz, 1 H), delta 7.49 (d, J = 9.5,1 H), delta 5.41 (q, J = 6.8 Hz, 1 H), delta 5.16 (br s, 1 H), delta 2.35 (s, 6H) MS calculated for C9H5CIF4N2O: 268.00 MS measured: 269 (M+H); 267 (M-H).

Reference： [1]Patent: WO2006/39243,2006,A1 .Location in patent: Page/Page column 103
[2]Patent: WO2006/39215,2006,A2 .Location in patent: Page/Page column 105

12
[ 684-07-1 ]
[ 76179-40-3 ]
1-(5,6-difluoro-1H-benzoimidazol-2-yl)-2,2,2-trifluoro-ethanol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride In water at 108℃; for 18h;	89 4,5-Difluoro-benzene-1,2-diamine (4.98 g; 34.5 mmoles) and 3,3,3-trifluoro-2-hydroxy-propionic acid (7.48 g; 51.9 mmoles) were suspended in 6N HCl (8 ml 48 mmoles) under a nitrogen atmosphere. The reaction was stirred vigorously and heated to 108°C for 18 hrs, then cooled to room temperature. The reaction was diluted with water (100 mL) and with ethyl acetate (100 mL), then sodium bicarbonate (6.05 g; 72.0 mmoles) was added slowly and in portions to quench the reaction. The aqueous layer was separated and extracted with ethyl acetate (3x40 mL). The extracts were combined, washed with water (30 mL) and brine (30 mL), then dried over Na2SO4. The filtrate was 5 concentrated in vacuo to yield a crude brown solid which was then purified by column chromatography (SiO2; 30% ethyl acetate/CH2Cl2) to yield the title compound as a pale orange solid. 1H NMR (400 MHz, CD3CN) δ 7.35 (m,1H), δ 7.21 (m,1 H), 65.44 (q, J = 6.8 Hz, 1 H) MS calculated for C9H5F5N2O: 252.03 MS measured: 253 (M+H); 251 (M-H).
	Stage #1: 3,3,3-trifluoro-2-hydroxy-propionic acid; 2-amino-4,5-difluoroaniline With hydrogenchloride In water at 108℃; for 18h; Stage #2: With sodium hydrogencarbonate In water; ethyl acetate	89 4,5-Difluoro-benzene-1 ,2-diamine (4.98 g; 34.5 mmoles) and 3,3,3- trifluoro-2-hydroxy-propionic acid (7.48 g; 51.9 mmoles) were suspended in 6N EPO HCI (8 ml 48 mmoles) under a nitrogen atmosphere. The reaction was stirred vigorously and heated to ,108°C for 18 hrs, then cooled to room temperature. The reaction was diluted with water (100 mL) and with ethyl acetate (100 ml_), then sodium bicarbonate (6.05 g; 72.0 mmoles) was added slowly and in portions to quench the reaction. The aqueous layer was separated and extracted with ethyl acetate (3x40 mL). The extracts were combined, washed with water (30 mL) and brine (30 mL), then dried over Na2SO4. The filtrate was concentrated in vacuo to yield a crude brown solid which was then purified by column chromatography (SiO2; 30% ethyl acetate/CH2CI2) to yield the title compound as a pale orange solid.1H NMR (400 MHz, CD3CN) δ 7.35 (m,1 H), δ 7.21 (m,1 H), δ 5.44 (q, J = 6.8 Hz, 1 H)MS calculated for C9H5F5N2O: 252.03 MS measured: 253 (M+H); 251 (M-H).

Reference： [1]Current Patent Assignee: JOHNSON & JOHNSON INC - WO2006/39243, 2006, A1 Location in patent: Page/Page column 104-105
[2]Current Patent Assignee: JOHNSON & JOHNSON INC - WO2006/39215, 2006, A2 Location in patent: Page/Page column 106-107

13
[ 684-07-1 ]
[ 95-83-0 ]
1-(5-chloro-1H-benzoimidazol-2-yl)-2,2,2-trifluoro-ethanol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride In water at 108℃; for 18h;	96 4-Chloro-benzene-1,2-diamine (2.02 g; 14.2 mmoles) and 3,3,3-trifluoro-2-hydroxy-propiqnic acid (3.10g; 21.5 mmoles) were suspended in 6N HCl (5 mL; 30 mmoles) and water (4 mL) under a nitrogen atmosphere. The reaction was stirred vigorously and heated to 108°C for 18 hrs, then cooled to room temperature. The reaction was diluted with water (400 mL) and with ethyl acetate (500 mL), then sodium bicarbonate (3.83 g; 45.6 mmoles) was added slowly and in portions to quench the reaction. The aqueous layer was separated and extracted with ethyl acetate (3x30 mL). The extracts were combined, washed with water (30 mL) and brine (30 mL), then dried over Na2SO4. The filtrate was concentrated in vacuo to yield a crude brown solid which was then purified by column chromatography (SiO2; 30% ethyl acetate/CH2Cl2) to yield the title compound as a tan solid. 1H NMR (400 MHz, CD3CN) δ 7.65 (n d, J = 1.5, 1 H), δ 7.58 (d, J = 8.6,1 H), δ 7.27 (dd, J = 6.6, 2.0, 3H) δ 5.42 (q, J = 6.9 Hz, 1 H) MS calculated for C9H6ClF3N2O: 250.01 MS measured: 251 , 253 (M+H); 249, 251 (M-H).
	Stage #1: 3,3,3-trifluoro-2-hydroxy-propionic acid; 4-Chloro-1,2-phenylenediamine With hydrogenchloride In water at 108℃; for 18h; Stage #2: With sodium hydrogencarbonate In water; ethyl acetate	96 4-Chloro-benzene-1 ,2-diamine (2.02 g; 14.2 mmoles) and 3,3,3-trifluoro-2-hydroxy-propionic acid (3.1Og; 21.5 mmoles) were suspended in 6N HCI (5 mL; 30 mmoles) and water (4 ml_) under a nitrogen atmosphere. The reaction was stirred vigorously and heated to 108°C for 18 hrs, then cooled to room temperature. The reaction was diluted with water (400 mL) and with ethyl acetate (500 mL), then sodium bicarbonate (3.83 g; 45.6 mmoles) was added slowly and in portions to quench the reaction. The aqueous layer was separated and extracted with ethyl acetate (3x30 mL). The extracts were combined, washed with water (30 mL) and brine (30 mL), then dried over Na2SO4. The filtrate was concentrated in vacuo to yield a crude brown solid which was then purified by column chromatography (SiO2; 30% ethyl acetate/CH2CI2) to yield the title compound as a tan solid.1H NMR (400 MHz, CD3CN) δ 7.65 (n d, J = 1.5, 1 H), δ 7.58 (d, J = 8.6, 1 H), δ 7.27 (dd, J = 6.6, 2.0, 3H) δ 5.42 (q, J = 6.9 Hz, 1 H) MS calculated for C9H6CIF3N2O: 250.01 MS measured: 251 , 253 (M+H); 249, 251 (M-H).

Reference： [1]Current Patent Assignee: JOHNSON & JOHNSON INC - WO2006/39243, 2006, A1 Location in patent: Page/Page column 109-110
[2]Current Patent Assignee: JOHNSON & JOHNSON INC - WO2006/39215, 2006, A2 Location in patent: Page/Page column 112

14
[ 684-07-1 ]
[ 32690-28-1 ]
1-(5,6-dinitro-1H-benzoimidazol-2-yl)-2,2,2-trifluoro-ethanol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride In water at 108℃; for 18h;	98 4,5-Dinitro-benzene-1,2-diamine (2.01 g; 10.2 mmoles) and 3,3,3-trifluoro-2-hydroxy-propionic acid (2.22 g; 15.4 mmoles) were suspended in 6N HCl (5 mL; 30 mmoles) and water (4 mL) under a nitrogen atmosphere. The reaction was stirred vigorously and heated to 108°C for 18 hrs, then cooled to room temperature. The reaction was diluted with water (40 mL) and with ethyl acetate (40 mL), then sodium bicarbonate (3.79 g; 45.0 mmoles) was added slowly and in portions to quench the reaction. The aqueous layer was separated and extracted with ethyl acetate (3x30 mL). The extracts were combined, washed with water (30 mL) and brine (40 mL), then dried over Na2SO4. The filtrate was concentrated in vacuo to yield a crude brown solid which was then purified by column chromatography (SiO2; 30% ethyl acetate/CH2Cl2) to yield the title compound as a brown solid. 1H NMR (400 MHz, CD3CN) δ 8.29 (s, 2H), δ 5.55 (q, J = 6.8, 1 H) MS calculated for C9H5F3N4O5: 306.16 MS measured: 305 (M-H).
	Stage #1: 3,3,3-trifluoro-2-hydroxy-propionic acid; 4,5-dinitro-1,2-phenylenediamine With hydrogenchloride In water at 108℃; for 18h; Stage #2: With sodium hydrogencarbonate In water; ethyl acetate	98 4,5-Dinitro-benzene-1 ,2-diamine (2.01 g; 10.2 mmoles) and 3,3,3- trifluoro-2-hydroxy-propionic acid (2.22 g; 15.4 mmoles) were suspended in 6N HCI (5 mL; 30 mmoles) and water (4 mL) under a nitrogen atmosphere. The reaction was stirred vigorously and heated to 108°C for 18 hrs, then cooled to room temperature. The reaction was diluted with water (40 mL) and with ethyl acetate (40 mL), then sodium bicarbonate (3.79 g; 45.0 mmoles) was added slowly and in portions to quench the reaction. The aqueous layer was separated and extracted with ethyl acetate (3x30 mL). The extracts were combined, washed with water (30 mL) and brine (40 mL), then dried over Na2SO4. The filtrate was concentrated in vacuo to yield a crude brown solid which was then purified by column chromatography (SiO2; 30% ethyl acetate/CH2CI2) to yield the title compound as a brown solid. EPO 1H NMR (400 MHz, CD3CN) δ 8.29 (s, 2H), δ 5.55 (q, J = 6.8, 1 H) MS calculated for C9H5F3N4O5: 306.16 MS measured: 305 (M-H).

Reference： [1]Current Patent Assignee: JOHNSON & JOHNSON INC - WO2006/39243, 2006, A1 Location in patent: Page/Page column 111
[2]Current Patent Assignee: JOHNSON & JOHNSON INC - WO2006/39215, 2006, A2 Location in patent: Page/Page column 113-114

15
[ 684-07-1 ]
[ 3171-45-7 ]
1-(5,6-dimethyl-1H-benzoimidazol-2-yl)-2,2,2-trifluoro-ethanol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride In water at 108℃; for 18h;	86 4,5-Dimethyl-benzene-1,2-diamine (5.04 g; 37.0 mmoles) and 3,3,3- trifluoro-2-hydroxy-propionic acid (8.01 g; 55.6 mmoles) were suspended in 6N HCl (9 mL; 54 mmoles) under a nitrogen atmosphere. The reaction was stirred vigorously and heated to 108°C for 18 hrs, then cooled to room temperature. The reaction was diluted with water (100 mL) and with ethyl acetate (100 mL), then sodium bicarbonate (6.90 g; 81.00 mmoles) was added slowly and in portions to quench the reaction. The aqueous layer was separated and extracted with ethyl acetate (3x40 mL). The extracts were combined, washed with water (30 mL) and brine (30 mL), then dried over Na2SO4- The filtrate was concentrated in vacuo to yield a crude brown solid which was purified by column chromatography (SiO2; 30% ethyl acetate/CH2Cl2) to yield the title compound as an off-white solid. 1H NMR (400 MHz, CD3CN) δ 10.51 (br s, 1 H), δ 7.37 (br d, 2H), δ 5.36,(q, J = 6.9 Hz, 1 H), δ 5.16 (br s, 1 H), δ 2.35 (s, 6H). MS calculated for CnHnF3N2O: 244.08 MS Measured: 245 (M+H); 243 (M-H).
	Stage #1: 3,3,3-trifluoro-2-hydroxy-propionic acid; 4,5-dimethyl-1,2-phenylenediamine With hydrogenchloride In water at 108℃; for 18h; Stage #2: With sodium hydrogencarbonate In water; ethyl acetate	86 4,5-Dimethyl-benzene-1 ,2-diamine (5.04 g; 37.0 mmoles) and 3,3,3- trifluoro-2-hydroxy-propionic acid (8.01 g; 55.6 mmoles) were suspended in 6N HCI (9 mL; 54 mmoles) under a nitrogen atmosphere. The reaction was stirred vigorously and heated to 1080C for 18 hrs, then cooled to room temperature. The reaction was diluted with water (100 mL) and with ethyl acetate (100 mL), then sodium bicarbonate (6.90 g; 81.00 mmoles) was added slowly and in EPO portions to quench the reaction. The aqueous layer was separated and extracted with ethyl acetate (3x40 ml_). The extracts were combined, washed with water (30 ml_) and brine (30 ml_), then dried over Na2SO4. The filtrate was concentrated in vacuo to yield a crude brown solid which was purified by column chromatography (SiO2; 30% ethyl acetate/CH2CI2) to yield the title compound as an off-white solid.1H NMR (400 MHz, CD3CN) δ 10.51 (br s, 1 H), δ 7.37 (br d, 2H)1 δ 5.36 (q, J = 6.9 Hz, 1 H), δ 5.16 (br s, 1 H), δ 2.35 (s, 6H).MS calculated for CnH11F3N2O: 244.08- MS Measured: 245 (M+H); 243 (M-H).

Reference： [1]Current Patent Assignee: JOHNSON & JOHNSON INC - WO2006/39243, 2006, A1 Location in patent: Page/Page column 102-103
[2]Current Patent Assignee: JOHNSON & JOHNSON INC - WO2006/39215, 2006, A2 Location in patent: Page/Page column 104-105

16
[ 882978-62-3 ]
[ 684-07-1 ]
2-(2,2,2-trifluoro-1-hydroxy-ethyl)-6-trifluoromethyl-1H-benzoimdazole-5-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride In water at 108℃; for 18h;	97 4,5-Diamino-2-trifluoromethyl-benzonitrile (4.14 g; 20.6 mmoles) and 3,3,3-trifluoro-2-hydroxy-propionic acid (4.50 g; 31.2 mmoles) were suspended in 6N HCl (7 mL; 42 mmoles) under a nitrogen atmosphere. The reaction was stirred vigorously and heated to 108°C for 18 hrs, then cooled to room temperature. The reaction was diluted with water (100 mL) and with ethyl acetate (100 mL), then sodium bicarbonate (5.19 g; 62.0 mmoles) was added slowly and in portions to quench the reaction. The aqueous layer was separated and extracted with ethyl acetate (3x40 mL). The extracts were combined, washed with water (30 mL) and brine (30 mL), then dried over Na2SO4. The filtrate was concentrated in vacuo to yield a crude dark solid which was then purified by column chromatography (SiO2; 30% ethyl acetate/CH2Cl2) to yield the title compound as a dark brown solid. 1H NMR (400 MHz, CD3CN) δ 8.27 (s, 1 H), δ 8.14 (s, 1 H), δ 5.54 (q, J = 6.9 Hz, 1 H) MS calculated for C11 H5F6N3O: 309.03 MS measured: 310 (M+H); 308 (M-H).
	Stage #1: 5-cyano-6-trifluoromethyl-1,2-phenylenediamine; 3,3,3-trifluoro-2-hydroxy-propionic acid With hydrogenchloride In water at 108℃; for 18h; Stage #2: With sodium hydrogencarbonate In water; ethyl acetate	97 4,5-Diamino-2-trifluoromethyl-benzonitrile (4.14 g; 20.6 mmoles) and3,3,3-trifluoro-2-hydroxy-propionic acid (4.50 g; 31.2 mmoles) were suspended EPO in 6N HCI (7 mL; 42 mmoles) under a nitrogen atmosphere., The reaction was stirred vigorously and heated to 108°C for 18 hrs, then cooled to room temperature. The reaction was diluted with water (100 mL) and with ethyl acetate (100 mL), then sodium bicarbonate (5.19 g; 62.0 mmoles) was added slowly and in portions to quench the reaction. The aqueous layer was separated and extracted with ethyl acetate (3x40 mL). The extracts were combined, washed with water (30 mL) and brine (30 mL), then dried over • Na2SO4. The filtrate was concentrated in vacuo to yield a crude dark solid which was then purified by column chromatography (SiO2; 30% ethyl acetate/CH2CI2) to yield the title compound as a dark brown solid.' 1H NMR (400 MHz, CD3CN) δ 8.27 (s, 1 H), δ 8.14 (s, 1 H), δ 5.54 (q, J = 6.9 Hz, 1 H)MS calculated for CnH5F6N3O: 309.03 MS measured: 310 (M+H); 308 (M-H).

Reference： [1]Current Patent Assignee: JOHNSON & JOHNSON INC - WO2006/39243, 2006, A1 Location in patent: Page/Page column 110-111
[2]Current Patent Assignee: JOHNSON & JOHNSON INC - WO2006/39215, 2006, A2 Location in patent: Page/Page column 112-113

17
[ 63155-04-4 ]
[ 684-07-1 ]
1-(5-chloro-6-methyl-1H-benzoimidazol-2-yl)-2,2,2-trifluoro-ethanol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride In water at 108℃; for 18h;	94 4-Chloro-5-methyl-benzene-1,2-diamine (5.06 g; 32.3 mmoles) and 3,3,3-trifluoro-2-hydroxy-propionic acid (7.11 g; 49.4 mmoles) were suspended in 6N HCl (12 mL; 72 mmoles) under a nitrogen atmosphere. The reaction was stirred vigorously and heated to 108°C for 18 hrs, then cooled to room temperature. The reaction was diluted with water (100 mL) and with ethyl acetate (100 mL), then sodium bicarbonate (9.12 g; 109 mmoles) was added slowly and in portions to quench the reaction. The aqueous layer was separated and extracted with ethyl acetate (3x40 mL). The extracts were combined, washed with water (30 mL) and brine (30 mL), then dried over Na2SO4. The filtrate was concentrated in vacuo to yield a crude brown solid which was then purified by column chromatography (SiO2; 30% ethyl acetate/CH2Cl2) to yield the title compound as a purple/brown solid. 1H NMR (400 ,MHz, CD3CN) δ 7.65 ( s, 1 H), δ 7.52 (s, 1 H), δ 5.40 (q, J = 6.9 Hz, 1 H), 62.46 (s, 3H) MS calculated for C10H8ClF3N2O: 264.03 MS measured: 265, 267 (M+H); 263, 265 (M-H).
	Stage #1: 4-chloro-5-methylbenzene-1,2-diamine; 3,3,3-trifluoro-2-hydroxy-propionic acid With hydrogenchloride In water at 108℃; for 18h; Stage #2: With sodium hydrogencarbonate In water; ethyl acetate	94 4-Chloro-5-methyl-benzene-1 ,2-diamine (5.06 g; 32.3 mmoles) and3,3,3-trifluoro-2-hydroxy-propionic acid (7.11 g; 49.4 mmoles) were suspended in 6N HCI (12 mL; 72 mmoles) under a nitrogen atmosphere. The reaction was stirred vigorously and heated to 108°C for 18 hrs, then cooled to room temperature. The reaction was diluted with water (100 mL) and with ethyl acetate (100 mL), then sodium bicarbonate (9.12 g; 109 mmoles) was added slowly and in portions to quench the reaction. The aqueous layer was separated and extracted with ethyl acetate (3x40 mL). The extracts were EPO combined, washed with water (30 ml_) and brine (30 mL), then dried over Na2SO4. The filtrate was, concentrated in vacuo to yield a crude brown solid which was then purified by column chromatography (SiO2; 30% ethyl acetate/CH2CI2) to yield the title compound as a purple/brown solid. ' 1H NMR (400 MHz, CD3CN) δ 7.65 ( s, 1 H), δ 7.52 (s, 1 H), δ 5.40 (q, J6.9 Hz, 1 H), δ 2.46 (s, 3H)MS calculated for Ci0H8CIF3N2O: 264.03MS measured: 265, 267 (M+H); 263, 265 (M-H).

Reference： [1]Current Patent Assignee: JOHNSON & JOHNSON INC - WO2006/39243, 2006, A1 Location in patent: Page/Page column 108-109
[2]Current Patent Assignee: JOHNSON & JOHNSON INC - WO2006/39215, 2006, A2 Location in patent: Page/Page column 110-111

18
[ 684-07-1 ]
[ 27841-33-4 ]
1-(5,6-dimethoxy-1H-benzoimidazol-2-yl)-2,2,2-trifluoro-ethanol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; In water; at 108℃; for 18h;	4,5-Dimethoxy-benzene-1,2-diamine (2.02 g; 12.0 mmoles) and 3,3,3-trifluoro-2-hydroxy-propionic acid (2.67 g; 18.5 mmoles) were suspended in 6N HCl (5 mL; 30 mmoles) and water (4 mL) under a nitrogen atmosphere. The reaction was stirred vigorously and heated to 108C for 18 hrs, then cooled to room temperature. The reaction was diluted with water (40 mL) and with ethyl acetate (40 mL), then sodium bicarbonate (3.84 g; 46.0 mmoles) was added slowly and in portions to quench the reaction. The aqueous layer was separated and extracted with ethyl acetate (3x30 mL). The extracts were combined, washed with water (30 mL) and brine (40 mL), then dried over Na2SO4. The filtrate was concentrated in vacuo to yield a crude dark orange solid which was then purified by column chromatography (SiO2; 30% ethyl acetate/CH2Cl2) to yield the title compound as a bright orange solid. 1H NMR (400 MHz, CD3CN) delta 7.15 (br s, 1 H), delta 7.06 <br s, 1 H), delta 5.34 (q, J = 6.8, 1 H) MS calculated for C11H11F3N2O3: 267.07 MS measured: 277 (M+H); 275 (M-H).
		4,5-Dimethoxy-benzene-1 ,2-diamine (2.02 g; 12.0 mmoles) and 3,3,3- trifluoro-2-hydroxy-propionic acid (2.67 g; 18.5 mmoles) were suspended in 6N HCI (5 ml 30 mmoles) and water (4 mL) under a nitrogen atmosphere. The reaction was stirred vigorously and heated to 108C for 18 hrs, then cooled to room temperature. The reaction was diluted with water (40 mL) and with ethyl acetate (40 mL), then sodium bicarbonate (3.84 g; 46.0 mmoles) was added slowly and in portions to quench the reaction. The aqueous layer was separated and extracted with ethyl acetate (3x30 mL). The extracts were combined, washed with water (30 mL) and brine (40 mL), then dried over Na2SO4. The filtrate was concentrated in vacuo to yield a crude dark orange solid which was then purified by column chromatography (SiO2; 30% ethyl acetate/CH2Cl2) to yield the title compound as a bright orange solid. 1H NMR (400 MHz, CD3CN) delta 7.15 (br s, 1 H), delta 7.06 (br s, 1 H), delta 5.34(q, J = 6.8, 1 H)MS calculated for CH HH F3N2O3: 267.07 MS measured: 277 (M+H); 275 (M-H).

Reference： [1]Patent: WO2006/39243,2006,A1 .Location in patent: Page/Page column 112
[2]Patent: WO2006/39215,2006,A2 .Location in patent: Page/Page column 114

19
[ 1044588-63-7 ]
[ 684-07-1 ]
[ 1044586-63-1 ]
[ 1044586-62-0 ]
[ 1044586-64-2 ]
[ 1044586-65-3 ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; triethylamine In dichloromethane at 20℃; for 16h;	176.C; 177.C; 178.C; 179.C Step C: N-r7-r2-Chloro-4-d.2.4-oxadiazol-3-vnphenyll-6-(4-chlorophenvn-2.2-dimethyl-3.4- dihvdro-2H-pyrano("2,3-61pyridin-4-yll-3,3,3-trifluoro-2-hvdroxypropanamide.; To a solution of the product of Step B (107 mg, 0.23 mmol), 3,3,3-trifluoro-2-hydroxypropionic acid (39 mg, 0.27 mmol), and NEt3 (63 μL, 0.45 mmol) in 10 mL of CH2Cl2 was added PyBOP (140 mg, 0.27 mmol). After stirring at rt for 16 h, the mixture was concentrated. Chromatography on a Biotage 25+M cartridge using 1 : 1 v/v EtOAc/hexanes as the eluant afforded two enantiomeric mixtures, which were subsequently resolved (the one having higher Rf value on TLC was resolved by AD using 13% EtOH/hex, and the other by AD using 20% IPA/hept) to afford the title compounds.

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2008/94473, 2008, A1 Location in patent: Page/Page column 69

20
[ 684-07-1 ]
[ 1177013-55-6 ]
[ 1177013-63-6 ]

Yield	Reaction Conditions	Operation in experiment
	With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 18h;	4 A mixture of the product of example Ik (50 mg), 3,3,3 -trifluorolactic acid (32 mg), DIPEA (90 μl) and BOP (114 mg) in dichloromethane (2.5 ml) was stirred for 18 h at room temperature. The reaction mixture was concentrated in vacuo and the residue was purified by preparative HPLC (10→90% acetonitrile; system 1).Yield: 17 mg. LC/MS-ESI: [M+H]+ = 592.3; anal. HPLC: R1 = 21.77 min (method 2); hFSHRago (CHO luc) EC50 = 1.3 nM

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2009/98283, 2009, A1 Location in patent: Page/Page column 37

21
[ 684-07-1 ]
[ 75-36-5 ]
[ 156816-81-8 ]

Yield	Reaction Conditions	Operation in experiment
85%	at 20℃;

Reference： [1]Location in patent: scheme or table Katagiri, Toshimasa; Handa, Michiharu; Asano, Hiroyuki; Asanuma, Teppei; Mori, Tomohiro; Jukurogi, Tatsuya; Uneyama, Kenji [Journal of Fluorine Chemistry, 2009, vol. 130, # 8, p. 714 - 717]

22
[ 684-07-1 ]
None [ No CAS ]
None [ No CAS ]

Reference： [1]Current Patent Assignee: CENTRAL GLASS CO LTD - US2004/49076, 2004, A1 Location in patent: Page 7

23
[ 684-07-1 ]
[ 62-53-3 ]
[ 1225204-19-2 ]

Yield	Reaction Conditions	Operation in experiment
43%	With 1-methyl-1H-imidazole; methanesulfonyl chloride In dichloromethane at 0℃; Inert atmosphere;

Reference： [1]Location in patent: experimental part Yasumoto, Manabu; Ueki, Hisanori; Soloshonok, Vadim A. [Journal of Fluorine Chemistry, 2010, vol. 131, # 2, p. 266 - 269]

24
[ 684-07-1 ]
[ 100-46-9 ]
[ 125969-76-8 ]

Yield	Reaction Conditions	Operation in experiment
44%	With 1-methyl-1H-imidazole; methanesulfonyl chloride In dichloromethane at 0℃; Inert atmosphere;

Reference： [1]Location in patent: experimental part Yasumoto, Manabu; Ueki, Hisanori; Soloshonok, Vadim A. [Journal of Fluorine Chemistry, 2010, vol. 131, # 2, p. 266 - 269]

25
[ 684-07-1 ]
[ 2627-86-3 ]
C₆H₉F₃O₃*C₈H₁₁N [ No CAS ]
C₆H₉F₃O₃*C₈H₁₁N [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In n-heptane; ethyl acetate at 60℃; for 0.5h; optical yield given as %ee;

Reference： [1]Location in patent: experimental part Yasumoto, Manabu; Ueki, Hisanori; Ono, Taizo; Katagiri, Toshimasa; Soloshonok, Vadim A. [Journal of Fluorine Chemistry, 2010, vol. 131, # 4, p. 535 - 539]

26
[ 684-07-1 ]
[ 67-63-0 ]
(R,S)-isopropyl 3,3,3-trifluoro-2-hydroxypropanoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sulfuric acid for 24h; Reflux;

Reference： [1]Location in patent: experimental part Yasumoto, Manabu; Ueki, Hisanori; Ono, Taizo; Katagiri, Toshimasa; Soloshonok, Vadim A. [Journal of Fluorine Chemistry, 2010, vol. 131, # 4, p. 535 - 539]

27
[ 1044583-53-0 ]
[ 684-07-1 ]
[ 1044590-64-8 ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; triethylamine In dichloromethane at 20℃;

Reference： [1]Location in patent: scheme or table Yan, Lin; Huo, Pei; Debenham, John S.; Madsen-Duggan, Christina B.; Lao, Julie; Chen, Richard Z.; Xiao, Jing Chen; Shen, Chun-Pyn; Stribling, D. Sloan; Shearman, Lauren P.; Strack, Alison M.; Tsou, Nancy; Ball, Richard G.; Wang, Junying; Tong, Xinchun; Bateman, Thomas J.; Reddy, Vijay B. G.; Fong, Tung M.; Hale, Jeffrey J. [Journal of Medicinal Chemistry, 2010, vol. 53, # 10, p. 4028 - 4037]

28
[ 684-07-1 ]
(3R,6R)-1-(2-(2H-1,2,3-triazol-2-yl)benzoyl)-6-methylpiperidine-3-carboximidamide [ No CAS ]
(1R)-2,2,2-trifluoro-1-{3-[(3R,6R)-6-methyl-1-[2-(2H-1,2,3-triazol-2-yl)phenyl]carbonyl}piperidin-3-yl]-1,2,4-oxadiazol-5-yl}ethanol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In 1,4-dioxane at 90℃; for 1h;	9.1 Step 1 : (2-(2H-1.2.3-Triazol-2-yl)phenyl)((2R.5R)-2-methyl-5-(5-(2.2.2-trifluoro-l- hydroxyethyl)- 1 ,2,4-oxadiazol-3 -yl)piperidin- 1 -yl)methanone (6) To a solution of (3R,6R)-l-(2-(2H- 1,2,3 -triazol-2-yl)benzoyl)-N-hydroxy-6- methylpiperidine-3-carboximidamide (100 mg, 0.31 mmol, Example 1, Step 5) in dioxane (2 mL) was added 3,3,3-trifluoro-2-hydroxypropanoic acid (132 mg, 0.915 mmol) and EDCl (291 mg, 1.52 mmol). The resulting mixture was stirred at 90°C for 1 h. After cooling to RT, the mixture was diluted with EtOAc (20 mL) and washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by prep-HPLC to give the title compound as an oil. LRMS m/z (M+H) 437.1 found, 437.2 required

Reference： [1]Current Patent Assignee: MERCK & CO INC; WUXI APPTEC CO., LTD. - WO2016/69510, 2016, A1 Location in patent: Page/Page column 53

29
[ 684-07-1 ]
4-{7-amino-[1,2,4]triazolo[1,5-a]pyridin-5-yl}-3-methylbenzonitrile [ No CAS ]
N-[5-(4-cyano-2-methylphenyl)-[1,2,4]triazolo[1,5-a]pyridin-7-yl]-3,3,3-trifluoro-2-hydroxypropanamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 3,3,3-trifluoro-2-hydroxy-propionic acid With bis(trichloromethyl) carbonate In tetrahydrofuran at 20℃; for 0.5h; Inert atmosphere; Stage #2: In tetrahydrofuran for 1.5h; Inert atmosphere; Stage #3: 4-{7-amino-[1,2,4]triazolo[1,5-a]pyridin-5-yl}-3-methylbenzonitrile In 1-methyl-pyrrolidin-2-one at 20 - 70℃; for 3h;	239 Example 239: N-[5-(4-Cyano-2-methylphenyl)-[1,2,4]triazolo[1,5-a]pyridin-7-yl]-3,3,3-trifluoro-2-hydroxypropanamide To a stirred solution of 3,3,3 -trifluoro-2-hydroxypropanoic acid (CAS 684-07-1, 0.1 16 g, 0.802 mmol) in anhydrous THF (2 mL) was added triphosgene (0.286 g, 0.963 mmol). The reaction mixture was stirred under nitrogen at room temperature for 30 mins. To the reaction mixture was added activated charcoal (0.005 g, 0.401 mmol) and the reaction was stirred for a further 1.5 h. The reaction mixture was evaporated to dryness and the residue was taken up in NMP (1.5 mL) and was passed through a PTFE filter into a stirred solution of 4-(7-amino-[1,2,4]triazolo[1,5-a]pyridin-5-yl)-3-methylbenzonitrile (Example 209, 0.100 g, 0.401 mmol) dissolved in NMP (0.5 mL). The reaction mixture was stirred at room temperature for 2h. The reaction mixture was then heated in a microwave at 70°C for 60 mins. MeOH (3 mL) was added and the reaction was concentrated in vacuo. The crude product was purified by reverse phase preparative HPLC eluted with acetonitrile / water (with 0.1% ammonia) to afford the title compound. lH NMR (400 MHz, DMSO-< 6) δ ppm 2.13 (s, 3 H), 4.82 - 4.98 (m, 1 H), 7.58 (d, J = 2 Hz, 1 H), 7.69 (d, J = 8 Hz, 1 H), 7.74 (d, J = 7 Hz, 1 H), 7.87 (d, J = 8 Hz, 1 H), 7.95 (s, 1 H), 8.34 - 8.43 (m, 2 H), 10.75 (s, 1 H) MS ES+: 376

Reference： [1]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - WO2016/148306, 2016, A1 Location in patent: Page/Page column 215-216

30
[ 684-07-1 ]
[ 563-76-8 ]
3-trifluorometh-yl-6-methyl-1,4-dioxane-2,5-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 3,3,3-trifluoro-2-hydroxy-propionic acid; α-bromopropionyl bromide at 75℃; for 12h; Inert atmosphere; Stage #2: With triethylamine In acetone for 6h; Reflux;	1 Preparation and Characterization of a Representative Cyclic Diester Monomer synthesis. Under an argon atmosphere, equal molar amounts of TFLA and 2-BPB were mixed and heated at 75 °C for 1 2 hours. The evolved HBr gas was directed to a saturated solution of NaHCO3 for neutralization. At the end of reaction time samples were cooled and dissolved in 100 ml dry acetone. Then two molarequivalents of triethylamine were added dropwise and the mixture was refluxed for 6 h. After filtration of triethylammonium salts, acetone was removed in vacuo and resulting product was dissolved in ethyl acetate and filtered through silica gel. Then solvent was distilled off and remaining product was analyzed by 1H NMR .Results2-BPB was first condensed with TFLA to form an intermediate ester, followed by ring closure under basic condition to yield the cyclic diester. The reaction was monitored by thin layer chromatography. ‘H NMR (300 IVIHz, CDC13) spectrum of crude reaction mixture of intermediate ester and cyclized monomer showed characteristic peaks related to both intermediate ester and cyclized monomer. Themethyl and methine protons can be identified as a doublet and quartet near 1.9 and4.5, respectively. The peak related to CF3 group in intermediate ester overlaps by the same group in cyclic dimer at 5.55 ppm. The formation of fluorine--substituted lactide was evaluated under varioussynthesis conditions by changing the time and temperature of the reaction (Table 1).Although increasing time and temperature of the synthesis was an attempt to derive thereaction toward formation of the monomer, no significant change in final products wasobserved. Similar ‘H NMR spectra were obtained for samples prepared at differentconditions, implying the flexibility and repeatability of t h e synthesis method. Inaddition, no additional byproducts were formed during step one of the reaction andobserved impurities were traces of starting materials.

Reference： [1]Current Patent Assignee: UNIVERSITY OF WASHINGTON - WO2016/134178, 2016, A1 Location in patent: Page/Page column 18; 19

31
[ 684-07-1 ]
N-hydroxy-7-(3-(morpholinomethyl)azetidin-1-yl)benzo[c][1,2,5]oxadiazole-5-carboximidamide [ No CAS ]
[ 96042-30-7 ]
2,2,2-trifluoro-1-(3-(7-(3-(morpholinomethyl)azetidin-1-yl)benzo[c][1,2,5]oxadiazol-5-yl)-1,2,4-oxadiazol-5-yl) ethan-1-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With dicyclohexyl-carbodiimide	Synthetic Methods DCC (618 mg, 3.0 mmol) was added to a solution of N-hydroxy-7-(3-(morpholinomethyl) azetidin-1-yl) benzo[c][1,2,5]oxadiazole-5-carboximidamide (500 mg, 1.5 mmol) and 3,3,3-trifluoro-lactic acid (432 mg, 3.0 mmol) in THF (20 ml) and DMF (30 ml) at room temperature. After the mixture was stirred 3 h, the reaction was heated to 70° C. for overnight. One more equivalent of DCC (309 mg, 1.5 mmol) and 3, 3, 3-trifluoro-lactic acid (216 mg, 1.5 mmol) were added to the reaction mixture and the reaction was stirred for 8 hours at this temperature. The reaction was added with EtOAc (60 ml). The mixture was washed with brine. The organic layer was dried and concentrated. The residue was purified via gradient elution (1:99, MeOH/DCM to 3:97, MeOH/DCM) to afford 2,2,2-trifluoro-1-(3-(7-(3-(morpholinomethyl)azetidin-1-yl)benzo[c][1,2,5]oxadiazol-5-yl)-1,2,4-oxadiazol-5-yl) ethan-1-ol TRV1644 (350 mg, 53%) as an orange solid. 1H NMR (400 MHz, CDCl3): 2.50-2.52 (m, 4H), 2.74 (d, J=7.5, 2H), 3.07-3.14 (m, 1H), 3.74-3.77 (m, 4H), 4.05 (d-d, J=5.5, J=8.5, 2H), 4.47 (t, J=8.3, 2H), 5.43 (q, J=5.9, 1H), 6.41 (s, 1H), 7.82 (s, 1H).

Reference： [1]Current Patent Assignee: TREVENTIS CORP - US2017/174641, 2017, A1

32
[ 21683-30-7 ]
[ 684-07-1 ]
N-(3,5-dimethyl-1-phenyl-1H-pyrazol-4-yl)-3,3,3-trifluoro-2-hydroxypropanamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
82 mg	With dmap; N-ethyl-N,N-diisopropylamine; dicyclohexyl-carbodiimide In acetonitrile at 20℃; for 24h;

Reference： [1]De Vita, Elena; Schüler, Peter; Lovell, Scott; Lohbeck, Jasmin; Kullmann, Sven; Rabinovich, Eitan; Sananes, Amiram; Heßling, Bernd; Hamon, Veronique; Papo, Niv; Hess, Jochen; Tate, Edward W.; Gunkel, Nikolas; Miller, Aubry K. [Journal of Medicinal Chemistry, 2018, vol. 61, # 19, p. 8859 - 8874]

33
[ 684-07-1 ]
2-((4-(trifluoromethyl)phenyl)amino)benzohydrazide [ No CAS ]
C₁₇H₁₃F₆N₃O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
45%	Stage #1: 3,3,3-trifluoro-2-hydroxy-propionic acid With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 10℃; for 0.166667h; Stage #2: 2-((4-(trifluoromethyl)phenyl)amino)benzohydrazide In N,N-dimethyl-formamide at 10℃; for 16h;	49.1 Step 1 : N'-(3,3,3-trifluoro-2-hydroxypropanoyl)-2-((4-(trifluoromethyl)phenyl)amino)benzo hydrazide To a solution of 51-la (268.3 mg, 1.86 mmol, 1.1 eq) and HATU (772.7 mg, 2.03 mmol, 1.2 eq) in DMF (5 mL) at 10 °C was added DIPEA (547.2 mg, 4.23 mmol, 0.7 mL, 2.5 eq). After stirring for 10 min, 51-1 (0.5 g, 1.69 mmol, 1 eq) was added and the resulting mixture was stirred at 10 °C for 16 h. LCMS showed no starting material was remained and 14% desired product was detected. The mixture was directly purified by prep-HPLC to give 51-2 (50 mg, 0.11 mmol, 45% yield. LCMS (ESI): RT = 0.797 min, mass calc for Ci7Hi3F6N303 421.09, m/z found 421.9[M+l]+. 1H NMR (400 MHz, CDCl3) d 8.98 (br s, 1H), 8.89 (br s, 1H), 8.52 (br s, 1H), 7.53 (d, J = 8.0 Hz, 1H), 7.47 (d, J= 8.5 Hz, 2H), 7.41 - 7.31 (m, 2H), 7.16 (d, J= 8.3 Hz, 2H), 6.86 (t, J= 7.8 Hz, 1H), 4.61 (br d, j= 7.0 Hz, 1H), 3.91 (br s, 1H).

Reference： [1]Current Patent Assignee: VIVACE THERAPEUTICS - WO2019/222431, 2019, A1 Location in patent: Paragraph 00316

34
[ 684-07-1 ]
[ 20989-17-7 ]
C₈H₁₁NO*C₃H₃F₃O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76%	In ethyl acetate at 60℃; for 2h;

Reference： [1]Wong, Lawrence W.-Y.; Vashchenko, Elena V.; Zhao, Ying; Sung, Herman H.-Y.; Vashchenko, Valerii V.; Mikhailenko, Vadim; Krivoshey, Alexander I.; Williams, Ian D. [Chirality, 2019, vol. 31, # 11, p. 979 - 991]

35
[ 684-07-1 ]
[ 2627-86-3 ]
C₈H₁₁N*C₃H₃F₃O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
69%	Stage #1: 3,3,3-trifluoro-2-hydroxy-propionic acid With (2S)-2-phenylglycinol In ethyl acetate at 60℃; for 2h; Stage #2: (<i>S</i>)-1-phenyl-ethylamine In water for 5h;

Reference： [1]Wong, Lawrence W.-Y.; Vashchenko, Elena V.; Zhao, Ying; Sung, Herman H.-Y.; Vashchenko, Valerii V.; Mikhailenko, Vadim; Krivoshey, Alexander I.; Williams, Ian D. [Chirality, 2019, vol. 31, # 11, p. 979 - 991]

36
[ 684-07-1 ]
[ 2627-86-3 ]
C₈H₁₁N*C₃H₃F₃O₃ [ No CAS ]
C₈H₁₁N*C₃H₃F₃O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1: 84% 2: 81%	In ethyl acetate for 2h; Inert atmosphere; Resolution of racemate; Reflux;

Reference： [1]Wong, Lawrence W.-Y.; Vashchenko, Elena V.; Zhao, Ying; Sung, Herman H.-Y.; Vashchenko, Valerii V.; Mikhailenko, Vadim; Krivoshey, Alexander I.; Williams, Ian D. [Chirality, 2019, vol. 31, # 11, p. 979 - 991]

37
[ 684-07-1 ]
[ 28143-91-1 ]
C₉H₁₃NO₂*C₃H₃F₃O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	In ethyl acetate at 60℃; for 2h;

Reference： [1]Wong, Lawrence W.-Y.; Vashchenko, Elena V.; Zhao, Ying; Sung, Herman H.-Y.; Vashchenko, Valerii V.; Mikhailenko, Vadim; Krivoshey, Alexander I.; Williams, Ian D. [Chirality, 2019, vol. 31, # 11, p. 979 - 991]

38
[ 684-07-1 ]
C₈₈H₆₆O₂P₄Pd₂⁽²⁺⁾*2BF₄^(1-) [ No CAS ]
C₄₇H₃₄F₃O₃P₂Pd⁽¹⁺⁾*BF₄^(1-) [ No CAS ]
C₄₇H₃₄F₃O₃P₂Pd⁽¹⁺⁾*BF₄^(1-) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium methylate In d⁽⁴⁾-methanol

Reference： [1]Chen, Zhongxiang; Yang, Mingxue; Sun, Zhaofeng; Zhang, Xuebo; Xu, Jing; Bian, Guangling; Song, Ling [Analytical Chemistry, 2019, vol. 91, # 22, p. 14591 - 14596]

39
[ 684-07-1 ]
[ 100-39-0 ]
3,3,3-trifluoro-2-hydroxypropanoic acid benzyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
55%	With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 5h; Cooling with ice; Inert atmosphere;	10 Synthesis of Compound 14 Combine trifluorolactic acid (3.5g, 24.3mmol, 1.0eq) and K2CO3 (5.0g, 36.5mmol, 1.5eq)Dissolve in dry 35mL DMF, add benzyl bromide (5.0g, 29.2mmol, 1.2eq) dropwise under ice water bath, protected by nitrogen, after adding, warm to room temperature and react for 5 hours. TLC detects that the reaction is complete.Quench with water, extract with dichloromethane (100mL×3), combine the organic phases,Wash with saturated brine successively, dry with anhydrous sodium sulfate, filter, and concentrate the filtrate under reduced pressure.The residue was purified by column chromatography to obtain compound 14 (3.14 g, 55%).
55%	With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 5h; Cooling with ice; Inert atmosphere;	10 Example 10 Synthesis of Compound 14 Trifluorolactic acid (3.5g, 24.3mmol, 1.0eq) and K2CO3 (5.0g, 36.5mmol, 1.5eq) were dissolved in dry 35mL DMF, and benzyl bromide (5.0g, 29.2mmol, 1.2eq) was added dropwise under an ice-water bath ), nitrogen protection, after the addition, the reaction was raised to room temperature for 5 hours, TLC detected that the reaction was complete, quenched by adding water, extracted with dichloromethane (100 mL × 3), the organic phases were combined, washed with saturated brine successively, and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by column chromatography to give compound 14 (3.14 g, 55%).

Reference： [1]Current Patent Assignee: SICHUAN BAILI PHARMACEUTICAL CO LTD - CN111689980, 2020, A Location in patent: Paragraph 0085-0087
[2]Current Patent Assignee: SICHUAN BAILI PHARMACEUTICAL CO LTD; BAILI BIO CHENGDU PHARMACEUTICAL - WO2022/56696, 2022, A1 Location in patent: Page/Page column 11

40
Exatecan mesylate [ No CAS ]
[ 684-07-1 ]
C₂₇H₂₃F₄N₃O₆ [ No CAS ]
C₂₇H₂₃F₄N₃O₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1: 32% 2: 36.7%	With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 3h;	9 Synthesis of Compounds 12 and 13 Compound 1 (Isinotecan mesylate) (40mg, 75.3mmol, 1.0eq)And trifluorolactic acid (16.3mg, 113.0 mmol, 1.5eq) dissolved in dry 5mL DMF,Then add PyBop (58.8mg, 113.0mmol, 1.5eq) and DIEA (15.7 uL, 113.0mmol, 1.5eq). After stirring at room temperature for 3 hours, TLC detected that the reaction was complete.Quench with water, extract with dichloromethane (10 mL×3), combine the organic phases,Dry over anhydrous sodium sulfate, filter, concentrate the filtrate under reduced pressure, and purify the residue by column chromatography.Compound 12 (13.5 mg, 32%) was obtained.

Reference： [1]Current Patent Assignee: SICHUAN BAILI PHARMACEUTICAL CO LTD - CN111689980, 2020, A Location in patent: Paragraph 0082-0084

41
[ 684-07-1 ]
[ 824-94-2 ]
4-methoxybenzyl 3,3,3-trifluoro-2-hydroxypropanoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
640 mg	With caesium carbonate In N,N-dimethyl-formamide at 20 - 70℃; for 23h;	26.1 Example 26 2-((4-(cyclohexyloxy)-2-methylene-4-oxobutanoyl)oxy)-3,3,3-trifluoropropanoic acid. Step 1. 1-(chloromethyl)-4-methoxybenzene (0.90 mL, 6.64 mmol) was added to a mixture of 3,3,3- trifluoro-2-hydroxypropanoic acid (1.00 g, 6.94 mmol) and cesium carbonate (2.26 g, 6.94 mmol) in dimethylformamide (30 mL). The mixture was stirred at RT for 3 h, then heated to 70 °C for 2 h, then cooled to RT and stirred for 18 h. The mixture was poured onto water (50 mL) and extracted with EtOAc (3 x 50 mL). The combined organic phases were washed with brine (100 mL), dried (MgSCL) and concentrated. The crude product was purified by chromatography on silica gel (0-50% EtOAc/isohexane) to afford 4-methoxybenzyl 3,3,3-trifluoro-2-hydroxypropanoate (640 mg, 2.30 mmol) as a colourless oil. [59] 1H NMR (400 MHz, DMSO-d6) d 7.36 - 7.30 (m, 2H), 7.14 (d, J = 7.4 Hz, 1H), 7.00 - 6.91 (m, 2H), 5.22 - 5.14 (m, 2H), 4.92 - 4.83 (m, 1H), 3.76 (s, 3H).

Reference： [1]Current Patent Assignee: SITRYX THERAPEUTICS - WO2020/222010, 2020, A1 Location in patent: Page/Page column 59

42
[ 684-07-1 ]
C₂₅H₂₄FN₃O₄ [ No CAS ]
C₂₈H₂₅F₄N₃O₆ [ No CAS ]
C₂₈H₂₅F₄N₃O₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1: Ca. 1.2 mg 2: 61%	With 4-methyl-morpholine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In ethanol; N,N-dimethyl-formamide at 0 - 20℃; for 2h;	7 Synthesis of compound 20 At room temperature, add compound 4 (3mg, 6.7umol) into a 10mL bottle, add 1mL absolute ethanol, 0.2mL DMF and 0.15mL NMM to dissolve, cool to 0 in an ice water bath, and add trifluorolactic acid (3.9mg , 4eq), 1-hydroxybenzotriazole HOBt (3.7mg, 4eq) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride EDCI (5.1mg, 4eq) After naturally warming to room temperature and reacting for 1 hour, the reaction solution was directly concentrated under reduced pressure, purified by preparative high performance liquid chromatography (acetonitrile/pure water system), the target peak was collected, and acetonitrile was removed under reduced pressure, and then lyophilized to obtain the compound 20A is about 1.2mg, yellow powdery solid, compound 20B is about 1.2mg, yellow powdery solid, yield is about 61%

Reference： [1]Current Patent Assignee: BAILI BIO CHENGDU PHARMACEUTICAL - CN112125915, 2020, A Location in patent: Paragraph 0326-0329

43
[ 684-07-1 ]
C₁₉H₁₈N₄*ClH [ No CAS ]
N-(5-(1-(4-ethylphenyl)-1H-pyrazol-4-yl)-1H-indol-3-yl)-3,3,3-trifluoro-2-hydroxypropanamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
12.9 mg	With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In dichloromethane at 20℃; for 4h;	59 Example 59: A-(5-(l-(4-ethylphenyl)-l//-pyrazol-4-yl)-l//-indol-3-yl)-3,3,3- trifluoro-2-hydroxypropanamide (Compound 166) 3,3,3-Trifluoro-2-hydroxypropanoic acid (114.3 mg, 0.8 mmol, 1.2 equiv.) was dissolved in DCM (10 mL), then DIEA (0.4 mL, 2.6 mmol, 4.0 equiv.), HATU (377.2 mg, 1.0 mmol, 1.5 equiv.) and 5-(l-(4-ethylphenyl)-li7-pyrazol-4-yl)-li7-indol-3-amine hydrogen chloride (224.1 mg, 0.7 mmol, 1.0 equiv.) were added. The reaction mixture was stirred for 4 hours at ambient temperature, then quenched by the addition of water. The resulting solution was extracted with DCM, dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was purified by Flash-Prep-HPLC with the following conditions: Column: XBridge Prep OBD C18 Column, 30x 150mm, 5pm; Mobile Phase A: Water (10 mM NH4HCC>3+0.1% NH4OH), Mobile Phase B: ACN; Flow rate: 60 mL/min; Gradient: 45%B to 75%B in 8 min; 254 nm; RT1: 7.23 min. This resulted in A-(5 -( 1 -(4-ethylphenyl)- liT-pyrazol-4-yl)- liT-indol-3 -yl)-3 ,3 , 3 -trifluoro-2- hydroxypropanamide (12.9 mg) as a yellow solid. LCMS Method D: [M+H]+= 429. NMR (400 MHz, DMSO-de) d 11.09 (s, 1H), 10.07 (s, 1H), 8.82 (s, 1H), 8.10 (s, 1H), 8.04 (s, 1H), 7.82 (d, 2H), 7.77 (d, 1H), 7.52-7.49 (m, 1H), 7.42-7.36 (m, 3H), 7.30 (d,1H), 4.88-4.85 (m, 1H), 2.67 (q, 2H), 1.24 (t, 3H).
12.9 mg	With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In dichloromethane at 20℃; for 4h;	59 Example 59: A-(5-(l-(4-ethylphenyl)-l//-pyrazol-4-yl)-l//-indol-3-yl)-3,3,3- trifluoro-2-hydroxypropanamide (Compound 166) 3,3,3-Trifluoro-2-hydroxypropanoic acid (114.3 mg, 0.8 mmol, 1.2 equiv.) was dissolved in DCM (10 mL), then DIEA (0.4 mL, 2.6 mmol, 4.0 equiv.), HATU (377.2 mg, 1.0 mmol, 1.5 equiv.) and 5-(l-(4-ethylphenyl)-li7-pyrazol-4-yl)-li7-indol-3-amine hydrogen chloride (224.1 mg, 0.7 mmol, 1.0 equiv.) were added. The reaction mixture was stirred for 4 hours at ambient temperature, then quenched by the addition of water. The resulting solution was extracted with DCM, dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was purified by Flash-Prep-HPLC with the following conditions: Column: XBridge Prep OBD C18 Column, 30x 150mm, 5pm; Mobile Phase A: Water (10 mM NH4HCC>3+0.1% NH4OH), Mobile Phase B: ACN; Flow rate: 60 mL/min; Gradient: 45%B to 75%B in 8 min; 254 nm; RT1: 7.23 min. This resulted in A-(5 -( 1 -(4-ethylphenyl)- liT-pyrazol-4-yl)- liT-indol-3 -yl)-3 ,3 , 3 -trifluoro-2- hydroxypropanamide (12.9 mg) as a yellow solid. LCMS Method D: [M+H]+= 429. NMR (400 MHz, DMSO-de) d 11.09 (s, 1H), 10.07 (s, 1H), 8.82 (s, 1H), 8.10 (s, 1H), 8.04 (s, 1H), 7.82 (d, 2H), 7.77 (d, 1H), 7.52-7.49 (m, 1H), 7.42-7.36 (m, 3H), 7.30 (d,1H), 4.88-4.85 (m, 1H), 2.67 (q, 2H), 1.24 (t, 3H).
12.9 mg	With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In dichloromethane at 20℃; for 4h;	59 Example 59: A-(5-(l-(4-ethylphenyl)-l//-pyrazol-4-yl)-l//-indol-3-yl)-3,3,3- trifluoro-2-hydroxypropanamide (Compound 166) 3,3,3-Trifluoro-2-hydroxypropanoic acid (114.3 mg, 0.8 mmol, 1.2 equiv.) was dissolved in DCM (10 mL), then DIEA (0.4 mL, 2.6 mmol, 4.0 equiv.), HATU (377.2 mg, 1.0 mmol, 1.5 equiv.) and 5-(l-(4-ethylphenyl)-li7-pyrazol-4-yl)-li7-indol-3-amine hydrogen chloride (224.1 mg, 0.7 mmol, 1.0 equiv.) were added. The reaction mixture was stirred for 4 hours at ambient temperature, then quenched by the addition of water. The resulting solution was extracted with DCM, dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was purified by Flash-Prep-HPLC with the following conditions: Column: XBridge Prep OBD C18 Column, 30x 150mm, 5pm; Mobile Phase A: Water (10 mM NH4HCC>3+0.1% NH4OH), Mobile Phase B: ACN; Flow rate: 60 mL/min; Gradient: 45%B to 75%B in 8 min; 254 nm; RT1: 7.23 min. This resulted in A-(5 -( 1 -(4-ethylphenyl)- liT-pyrazol-4-yl)- liT-indol-3 -yl)-3 ,3 , 3 -trifluoro-2- hydroxypropanamide (12.9 mg) as a yellow solid. LCMS Method D: [M+H]+= 429. NMR (400 MHz, DMSO-de) d 11.09 (s, 1H), 10.07 (s, 1H), 8.82 (s, 1H), 8.10 (s, 1H), 8.04 (s, 1H), 7.82 (d, 2H), 7.77 (d, 1H), 7.52-7.49 (m, 1H), 7.42-7.36 (m, 3H), 7.30 (d,1H), 4.88-4.85 (m, 1H), 2.67 (q, 2H), 1.24 (t, 3H).

Reference： [1]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - WO2022/15979, 2022, A1 Location in patent: Page/Page column 146-147
[2]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - WO2022/15979, 2022, A1 Location in patent: Page/Page column 146-147
[3]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - WO2022/15979, 2022, A1 Location in patent: Page/Page column 146-147

44
[ 684-07-1 ]
C₂₄H₂₂FN₃O₄*CH₄O₃S [ No CAS ]
C₂₇H₂₃F₄N₃O₆ [ No CAS ]
C₂₇H₂₃F₄N₃O₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
32%	With benzotriazole-1-yl-oxy-tris-pyrrolidino-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 3h;	9 Example 9 Synthesis of Compounds 12 and 13 Compound 1 (ixitecan mesylate) (40mg, 75.3mmol, 1.0eq) and trifluorolactic acid (16.3mg, 113.0mmol, 1.5eq) were dissolved in dry 5mL DMF, and PyBop (58.8mg, 113.0eq) was added mmol, 1.5eq) and DIEA (15.7uL, 113.0mmol, 1.5eq). After stirring at room temperature for 3 hours, TLC detected that the reaction was complete, quenched with water, extracted with dichloromethane (10 mL×3), combined the organic phases, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography to obtain Compound 12 (13.5 mg, 32%).

Reference： [1]Current Patent Assignee: SICHUAN BAILI PHARMACEUTICAL CO LTD; BAILI BIO CHENGDU PHARMACEUTICAL - WO2022/56696, 2022, A1 Location in patent: Page/Page column 10-11

Type	HazMat fee for 500 gram (Estimated)
Excepted Quantity	USD 0.00
Limited Quantity	USD 15-60
Inaccessible (Haz class 6.1), Domestic	USD 80+
Inaccessible (Haz class 6.1), International	USD 150+
Accessible (Haz class 3, 4, 5 or 8), Domestic	USD 100+
Accessible (Haz class 3, 4, 5 or 8), International	USD 200+

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
{[ item.p_purity ]}	{[ item.pr_size ]}	{[ getRatePrice(item.pr_usd, 1,1) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]}	{[ getRatePrice(item.pr_usd, 1,1) ]}	Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate) ]}	{[ item.pr_usastock ]}	Inquiry -	{[ item.pr_chinastock ]}	Inquiry -

CAS No. :	684-07-1	MDL No. :	MFCD00051802
Formula :	C₃H₃F₃O₃	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	-
M.W :	144.05	Pubchem ID :	-
Synonyms :

Signal Word:	Danger	Class:	8
Precautionary Statements:	P260-P264-P271-P280-P301+P330+P331-P303+P361+P353-P304+P340-P305+P351+P338-P310-P363-P403+P233-P405-P501	UN#:	3261
Hazard Statements:	H335-H314	Packing Group:	Ⅱ
GHS Pictogram:

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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

[ CAS No. 684-07-1 ] {[proInfo.proName]}

Quality Control of [ 684-07-1 ]

Related Doc. of [ 684-07-1 ]

Product Details of [ 684-07-1 ]

Safety of [ 684-07-1 ]

Application In Synthesis of [ 684-07-1 ]

[ 684-07-1 ] Synthesis Path-Downstream 1~44

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry