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[ CAS No. 147688-58-2 ] {[proInfo.proName]}

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3d Animation Molecule Structure of 147688-58-2
Chemical Structure| 147688-58-2
Chemical Structure| 147688-58-2
Structure of 147688-58-2 * Storage: {[proInfo.prStorage]}
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Product Details of [ 147688-58-2 ]

CAS No. :147688-58-2 MDL No. :MFCD09701959
Formula : C6H13NO Boiling Point : -
Linear Structure Formula :- InChI Key :UFLFSJVTFSZTKX-UHFFFAOYSA-N
M.W : 115.17 Pubchem ID :18959674
Synonyms :

Calculated chemistry of [ 147688-58-2 ]

Physicochemical Properties

Num. heavy atoms : 8
Num. arom. heavy atoms : 0
Fraction Csp3 : 1.0
Num. rotatable bonds : 0
Num. H-bond acceptors : 2.0
Num. H-bond donors : 1.0
Molar Refractivity : 36.68
TPSA : 21.26 Ų

Pharmacokinetics

GI absorption : Low
BBB permeant : No
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -6.97 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.83
Log Po/w (XLOGP3) : 0.04
Log Po/w (WLOGP) : 0.0
Log Po/w (MLOGP) : 0.21
Log Po/w (SILICOS-IT) : 1.43
Consensus Log Po/w : 0.7

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 1.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -0.58
Solubility : 30.3 mg/ml ; 0.263 mol/l
Class : Very soluble
Log S (Ali) : -0.04
Solubility : 105.0 mg/ml ; 0.914 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -1.49
Solubility : 3.74 mg/ml ; 0.0324 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.24

Safety of [ 147688-58-2 ]

Signal Word:Warning Class:
Precautionary Statements:P280-P305+P351+P338 UN#:
Hazard Statements:H317-H319 Packing Group:
GHS Pictogram:

Application In Synthesis of [ 147688-58-2 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 147688-58-2 ]

[ 147688-58-2 ] Synthesis Path-Downstream   1~69

  • 1
  • [ 167947-19-5 ]
  • [ 147688-58-2 ]
  • (2S,3S,5S,8R,9S,10S,13S,14S,17S)-2-(2,2-Dimethyl-morpholin-4-yl)-17-(2-hydroxymethyl-[1,3]dioxolan-2-yl)-10,13-dimethyl-hexadecahydro-cyclopenta[a]phenanthren-3-ol [ No CAS ]
  • 2
  • [ 167947-19-5 ]
  • [ 147688-58-2 ]
  • [ 167947-21-9 ]
  • 3
  • [ 167947-15-1 ]
  • [ 147688-58-2 ]
  • (2S,3S,5S,8S,9S,10S,13S,14S,17S)-2-(2,2-Dimethyl-morpholin-4-yl)-3-hydroxy-17-(2-hydroxymethyl-[1,3]dioxolan-2-yl)-10,13-dimethyl-hexadecahydro-cyclopenta[a]phenanthren-11-one [ No CAS ]
  • 4
  • [ 167947-15-1 ]
  • [ 147688-58-2 ]
  • (2β,3α,5α)-3,21-dihydroxy-2-(2,2-dimethyl-4-morpholinyl)pregnane-11,20-dione [ No CAS ]
  • 5
  • [ 147688-58-2 ]
  • [ 503469-20-3 ]
  • 2-(2,2-dimethyl-morpholin-4-yl)-benzo[<i>h</i>]chromen-4-one [ No CAS ]
  • 6
  • [ 147688-58-2 ]
  • [ 42398-55-0 ]
  • 2-(2,2-dimethyl-morpholin-4-yl)-pyrimido[2,1-<i>a</i>]isoquinolin-4-one [ No CAS ]
  • 7
  • [ 693286-14-5 ]
  • [ 147688-58-2 ]
  • [ 693286-12-3 ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; In acetonitrile; at 20℃; for 16h; A mixture OF 4-CHLORO-3-CHLOROMETHYL-6- (2, 6-diethyl-phenyl) -2-methyl-pyridine (310 mg, 1.0 mmol), <strong>[147688-58-2]2,2-<strong>[147688-58-2]dimethyl-morpholine</strong></strong> (150 mg, 1.3 mmol) and K2C03 (417 mg, 3 mmol) in CH3CN (10 mL) is stirred at room temperature for 16 hours. EtOAc (20 mL) and water (20 mL) are added to the mixture. The organic layer is separated, washed once with brine, dried (Na2SO4) and concentrated to give the title compound.
  • 8
  • [ 22118-09-8 ]
  • [ 147688-58-2 ]
  • 2-bromo-1-(2,2-dimethyl-morpholin-4-yl)-ethanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
56% With triethylamine; In dichloromethane; at -10 - 20℃; EXAMPLE 76: (S)-4- [2- (3, 3-Dimethyl-morpholin-4-yl) -2-oxo- ETHYL-6, 6-<strong>[147688-58-2]dimethyl-morpholine</strong>-3-carboxylic acid (6-chloro- 9H-BETA-CARBOLIN-8-YL)-AMIDE-BIS-HYDROCHLORIDE salt --152-- [00245] 2, 2-DIMETHYLMORPHOLINE (3.0 g, 26.1 mmol) (prepared according to the procedure of Cottle, D. L. , et AL. J. ORG. Chem. 1946, 11, 286-291) was dissolved in dichloromethane (60 mL). Triethylamine (3.6 mL, 2.66 g, 26.1 mmol) was added and the reaction was cooled TO-10C. Bromoacetyl chloride (2.2 mL, 4.08 g, 26.1 mmol) was added dropwise and the solution was warmed slowly to room temperature. The reaction was concentrated to dryness in vacuo, redissolved in ethyl acetate and passed through a plug of silica gel. The eluant was concentrated to a yellow oil (3.45 g, 56%) that was carried to the next step. Retention Time (LC, method: ammonium acetate standard): 1.20 min. MS (M+H+) : 237.
  • 9
  • [ 141-46-8 ]
  • [ 147688-58-2 ]
  • [ 83497-79-4 ]
YieldReaction ConditionsOperation in experiment
Dissolve <strong>[147688-58-2]2,2-<strong>[147688-58-2]dimethylmorpholine</strong></strong> (151 mg, 1.0 rnmol) in 1,2-dichloroethane (3 mL) and add glycolaldehyde (60 mg, 1.0 mmol). Stir at room temperature for 30 min followed by addition of NaBH(OAc)3 (233 mg, 1.1 mmol). Stir 3 h, then quench by adding 30 mL of IN NaOH. Pour into a separatory funnel and extract with EtOAc (2 x 50 mL). Wash the combined organic layers with brine (50 mL). The crude alcohol was used as is without further purification. MS (ES+) 160.2 (M+ 1)+.
YieldReaction ConditionsOperation in experiment
62% To the cis-trityltetrazole (1.598 g, 2.70 mmol) in 8.0 mL of THF was added 3N HCl (4.0 mL) at room temperature. After 43 h at room temperature, the mixture was extracted with Et2 O, adjusted to pH 6, then extracted with CH2 Cl2. The combined extracts were dried over Na2 SO4 and concentrated to give a white solid. Recrystallization from CH2 Cl2 gave a solid which was taken up in EtOH and concentrated to give the cis-dimethyl morpholine (0.584 g, 62%), a white powder, as the corresponding hydrochloride salt. 1 H NMR (CDCl3): delta1.19 (6H, d, J=6.2 Hz), 2.43 (2H, t, J=11.1 Hz), 3.35 (2H, d, J=11.5 Hz), 4.10 (2H, s), 4.25 (2H, m), 7.10 (2H, d, J=7.9 Hz), 7.40-7.61 (5H, m), 7.82 (1H, d, J=6.4 Hz). MS (DCl): m/z 350 (MH+). mp: 230-231 C. Anal. Calcd. for C20 H23 N5 O.HCl.1/4 H2 O: C, 61.53; H, 6.33; N, 17.94. Found: C, 61.54; H, 6.24; N, 17.90. STR18
  • 11
  • [ 589-15-1 ]
  • [ 147688-58-2 ]
  • [ 1200131-22-1 ]
YieldReaction ConditionsOperation in experiment
97% With potassium carbonate; In acetonitrile; at 85℃; for 20h; A mixture of 4-bromobenzyl bromide (1.5 g, 6.0 mmol), <strong>[147688-58-2]2,2-<strong>[147688-58-2]dimethylmorpholine</strong></strong>(0.69 g, 6.0 mmol) and potassium carbonate (0.99 g, 7.2 mmol) in acetonitrile (60 mL) was heated at 85 C for 20 h. The mixture was allowed to cool to ambient temperature and the solid was removed by filtration and the filtrate evaporated. The resultant residue was dissolved in DCM/ methanol and loaded onto a 20 g SCX-2 cartridge which was washed with methanol then 2N ammonia in methanol. Concentration of the combined basic fractions afforded the title compound (1.65 g, 97%) as an orange oil. 1H NMR (CDCl3, 300MHz): 7.44 (d, J = 8.0Hz, 2H), 7.22 (d, J = 8.0Hz, 2H), 3.75 (t, J = 4.8Hz, 2H), 3.39 (s, 2H), 2.37 (t, J = 4.6Hz, 2H), 2.16 (s, 2H), 1.23 (s, 6H).
  • 12
  • [ 1245464-62-3 ]
  • [ 147688-58-2 ]
  • [ 1245465-20-6 ]
YieldReaction ConditionsOperation in experiment
To a solution of 6-bromo-4-[5-(chloromethyl)-1 ,3,4-oxadiazol-2-yl]-1-(phenylsulfonyl)-1 H- indazole (200 mg, 0.441 mmol) in acetonitrile (2 ml) was added <strong>[147688-58-2]2,2-<strong>[147688-58-2]dimethylmorpholine</strong></strong> (102 mg, 0.882 mmol, available from Chembridge Corporation) and the mixture heated at 70 0C for 18 hr. The mixture was cooled to room temperature and a further portion of 2,2- <strong>[147688-58-2]dimethylmorpholine</strong> (102 mg, 0.882 mmol), DIPEA (0.154 ml_, 0.882 mmol) and sodium iodide (66.1 mg, 0.441 mmol) were added. The mixture was then heated again at 70 0C for 2 hours. The mixture was cooled to room temperature, diluted with DCM and washed with water. The organic layer was separated through a hydrophobic frit and the solvent removed in vacuo. The resulting yellow oil was dried in a vacuum oven at 6O0C overnight to give a pale yellow solid, which was dissolved in DCM (10 ml) and washed with dilute HCI (10 ml) followed by water (10 ml), separating the layers using a hydrophobic frit. The DCM was removed in vacuo to give the title compound as a cream solid (214 mg). LCMS (Method A) R1 = 1.25 min, MH+ 534.
214 mg 6-Bromo-4-{5-[(2,2-dimethyl-4-morpholinyl)methyl]-1,3,4-oxadiazol-2-yl}-1-(phenylsulfonyl)-1H-indazole To a solution of 6-bromo-4-[5-(chloromethyl)-1,3,4-oxadiazol-2-yl]-1-(phenylsulfonyl)-1H-indazole (200 mg, 0.441 mmol) in acetonitrile (2 ml) was added <strong>[147688-58-2]2,2-<strong>[147688-58-2]dimethylmorpholine</strong></strong> (102 mg, 0.882 mmol, available from Chembridge Corporation) and the mixture heated at 70 C. for 18 hr. The mixture was cooled to room temperature and a further portion of <strong>[147688-58-2]2,2-<strong>[147688-58-2]dimethylmorpholine</strong></strong> (102 mg, 0.882 mmol), DIPEA (0.154 mL, 0.882 mmol) and sodium iodide (66.1 mg, 0.441 mmol) were added. The mixture was then heated again at 70 C. for 2 hours. The mixture was cooled to room temperature, diluted with DCM and washed with water. The organic layer was separated through a hydrophobic frit and the solvent removed in vacuo. The resulting yellow oil was dried in a vacuum oven at 60 C. overnight to give a pale yellow solid, which was dissolved in DCM (10 ml) and washed with dilute HCl (10 ml) followed by water (10 ml), separating the layers using a hydrophobic frit. The DCM was removed in vacuo to give the title compound as a cream solid (214 mg). ECMS (Method A) R=1.25 mi MH+ 534.
  • 13
  • [ 1094070-55-9 ]
  • [ 147688-58-2 ]
  • [ 1258277-11-0 ]
  • 14
  • [ 67443-38-3 ]
  • [ 147688-58-2 ]
  • [ 1259440-06-6 ]
YieldReaction ConditionsOperation in experiment
In dimethyl sulfoxide; at 60℃; for 2.5h; 4-(5-Bromo-3-nitropyridin-2-yl)-<strong>[147688-58-2]2,2-<strong>[147688-58-2]dimethylmorpholine</strong></strong> To a 100 mL round bottom flask containing 5-bromo-2-chloro-3-nitropyridine (2.00 g, 8.43 mmol) in DMSO (10 mL) was added <strong>[147688-58-2]2,2-<strong>[147688-58-2]dimethylmorpholine</strong></strong> (commercially available from ChemBridge Corporation) (1.9 mL, 16.9 mmol) dropwise. The reaction was heated to 60 C. and monitored with TLC and LC-MS. After 2.5 h, LC-MS showed that the reaction was complete. The mixture was cooled to rt then diluted with water. After extracting three times with EtOAc, the organic layers were combined then washed with brine and dried over anhydrous magnesium sulfate. After filtration, the mixture was concentrated under reduced pressure to afford an orange oil as 4-(5-bromo-3-nitropyridin-2-yl)-<strong>[147688-58-2]2,2-<strong>[147688-58-2]dimethylmorpholine</strong></strong>. 1H NMR (400 MHz, CDCl3) delta ppm 8.34 (1H, d, J=2.2 Hz), 8.25 (1H, d, J=2.2 Hz), 3.87 (2H, m), 3.36 (4H, m), 1.26 (6H, s).
  • 15
  • [ 1259439-03-6 ]
  • [ 147688-58-2 ]
  • [ 1259440-49-7 ]
YieldReaction ConditionsOperation in experiment
With sodium t-butanolate;tris-(dibenzylideneacetone)dipalladium(0); 2-dicyclohexylphosphino-2,4,6-triisopropylbiphenyl; In toluene;Reflux; 2,2-Dimethyl-4-(6-morpholino-5-nitropyridin-3-yl)morpholine A solution of 4-(5-chloro-3-nitropyridin-2-yl)morpholine (850 mg, 3.49 mmol; described herein), <strong>[147688-58-2]2,2-<strong>[147688-58-2]dimethylmorpholine</strong></strong> (480 muL, 4180 mumol), tris(dibenzylideneacetone)dipalladium(o) (224 mg, 0.244 mmol), 2-(dicyclohexylphosphino)-2,4,6,-tri-i-propyl-1,1-biphenyl (249 mg, 0.523 mmol), sodium 2-methylpropan-2-olate (671 mg, 6.98 mmol), and toluene (517 mL) was refluxed overnight, then cooled to rt and concentrated. The resulting residue was taken up in EtOAc, washed with satd aq. sodium bicarbonate and brine, then the organic layer dried (magnesium sulfate) and concentrated. Column chromatography afforded 2,2-dimethyl-4-(6-morpholino-5-nitropyridin-3-yl)morpholine as a red solid. Mass Spectrum (ESI) m/e=323.2 (M+1).
  • 16
  • [ 1259439-39-8 ]
  • [ 147688-58-2 ]
  • [ 1259514-33-4 ]
YieldReaction ConditionsOperation in experiment
In isopropyl alcohol; at 120℃; for 5h;Microwave irradiation; 2,4-dichloro-5,7-difluoro-3-methylquinoline (1.0 g, 4.03 mmol) and 2,2-dimethyl- morpholine (0.46 mL, 4.03 mmol) were slurried in 2-propanol (10 mL) and heated in a microwave reactor at 120 C for 5 h. The reaction was then concentrated to dryness and purified by column chromatography (hexanes : EtOAc, 1 :0 to 1 : 1) to give 4-(4-chloro-5,7-difluoro-3-methylquinolin-2-yl)-<strong>[147688-58-2]2,2-<strong>[147688-58-2]dimethylmorpholine</strong></strong>. 1H NMR (400 MHz, chloroform-;/) delta ppm 7.31 (1 H, ddd, J=9.7, 2.7, 1.5 Hz), 6.89 (1 H, ddd, J=12.3, 8.9, 2.5 Hz), 3.93 - 3.98 (2 H, m), 3.23 - 3.28 (2 H, m), 3.10 (2 H, s), 2.47 (3 H, s), 1.37 (6 H, s). Mass Spectrum (ESI) m/e = 327.2 (M +I)-
  • 17
  • [ 147688-58-2 ]
  • [ 1215867-65-4 ]
  • 18
  • [ 147688-58-2 ]
  • [ 1215867-62-1 ]
  • 19
  • [ 1215867-42-7 ]
  • [ 147688-58-2 ]
  • [ 1215867-41-6 ]
YieldReaction ConditionsOperation in experiment
With lithium hexamethyldisilazane;tris-(dibenzylideneacetone)dipalladium(0); DavePhos; at 75℃; for 2h;Inert atmosphere; Sealed; Step 2: A vial was charged with (S)-3-bromo-7-(2-fluoropyridin-3-yl)-5'H- spiro[chromeno[2,3-b]pyridine-5,4'-oxazol]-2'-amine (110 mg, 0.257 mmol), DavePhos (12.16 mg, 0.031 mmol), and tris(dibenzylideneacetone)dipalladium(0) (11.79 mg, 0.013 mmol). The vessel was flushed with Ar(g), then lithium bis(trimethylsilyl)amide (772 xL, 0.772 mmol) (1.0 M solution in THF) and <strong>[147688-58-2]2,2-<strong>[147688-58-2]dimethylmorpholine</strong></strong> (61.8 mu, 0.515 mmol) were added in sequence. The vial was sealed and placed in a 75 C oil bath for two hours. The mixture was diluted with saturated aq. ammonium chloride solution (20 mL) and water (10 mL). The mixture was extracted with DCM (3 x 20 mL), leaving behing a dark oily solid. The combined organic extracts were dried over sodium sulfate, filtered, and evaporated. The residue was chromatographed on an 24-g Redi-Sep Gold column with 0-70% of a 90: 10:1 mix of DCM/MeOH/NH4OH in DCM to give (S)-3-(2,2- dimethylmo holino)-7-(2-fluoropyridin-3-yl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'- oxazol]-2'-amine as a yellow solid.
  • 20
  • [ 1215867-63-2 ]
  • [ 147688-58-2 ]
  • [ 1215867-64-3 ]
YieldReaction ConditionsOperation in experiment
With lithium hexamethyldisilazane;tris-(dibenzylideneacetone)dipalladium(0); DavePhos; In tetrahydrofuran; at 110℃; for 1h;Inert atmosphere; Sealed; Microwave irradiation; Example 32 (Method AA16)Synthesis of (S)-2'-(2,2-dimethylmorpholino)-7'-(2-fluoropyridin-3-yl)-5H- spiro[oxazole-4,9'-xanthen]-2-amineStep 1 : A 2-5 ml microwave vial was charged with (S)-2-amino-2'-bromo-5H- spiro[oxazole-4,9'-xanthen]-7'-ol (300 mg, 0.864 mmol) (104780-26-0), Pd2dba3 (39.6 mg, 0.043 mmol), 2'-(dicyclohexylphosphino)-N,N-dimethylbiphenyl-2-amine (40.8 mg, 0.104 mmol) and 2,2-cUmethylrnorpholine (299 mg, 2.59 mmol). The mixture was capped with argon and LiHMDS (1M in THF) (4321 L, 4.32 mmol) was added and the vial was sealed and heated at 110 C in microwave reactor for 1 hr. The reaction mixture was quenched by addition of 2 ml water and EtOAc, then saturated NH4C1 was added. The organic layer was filterd through Celite, concentrated in vacuo and purified on a 40g RediSep column using 15-80% DCM/MeOH/NH40H in DCM to afford (R)-2-amino-2'- (2,2-dimethylmo holino)-5H-spiro[oxazole-4,9'-xanthen]-7'-ol.
  • 21
  • [ 1365839-26-4 ]
  • [ 147688-58-2 ]
  • C28H39N7O3S [ No CAS ]
YieldReaction ConditionsOperation in experiment
Example 79:W-(1 -acryloyl-4-piperidinyi)-4-[(2,2-dimethyl-4-morpholinyl)methyl3-W'- [1 ,3]thiazolo[5,4-fe]pyridin-2-yl-2,6-pyridinediamineA solution of 1 , 1 -dimethylethyl 4-[4-formyi-6-([1 ,3]thiazolo[5,4-/}]pyridin-2-ylamino)-2- pyridinyl]amino}-1 -pipendinecarboxylate (50 mg, 0.1 1 mmol) in tetrahydrofuran (0.5 mL) was treated with 2,2-dimethylmorpho.ine (25.3 mg, 0.22 mmol) and the reaction mixture was stirred for 15 minutes. The mixture was then treated with dichloromethane (2 mL) and sodium tnacetoxyborohydride (46.6 mg, 0.22 mmol). The reaction mixture was stirred for 16 hours. Saturated aqueous sodium bicarbonate (1 mL) was added and the reaction was stirred for 30 minutes. Dichloromethane (5 mL) was added and the phases were separated. The organic extract was dried using a hydrophobic frit and evaporated to dryness. A round bottom flask was charged with the obtained solid, 4 HCI in dioxane (1.072 mL, 4.29 mmol), dichloromethane (3 mL) and methanol (2 mL). The reaction was stirred at room temperature for 1 hour. The solvent was evaporated to dryness. The residue was dissolved in /V-methyl-2-pyrrolidone (1 mL) and treated with N,N- diisopropylethyiamine (0.095 mL, 0.545 mmol) and 2-propenoyl chloride (0.018 mL, 0.218 mmol). The reaction was stirred at room temperature for 1 hour. The mixture was subjected to purification by mass directed automated preparative HPLC (ammonium bicarbonate modifier) to afford the title compound (27 mg, 0.053 mmol, 48 % yield) as a light brown solid. LCMS (Method D): Rt 0.99 minutes; m/z 508 (MH+).
  • 22
  • [ 1365839-29-7 ]
  • [ 147688-58-2 ]
  • C27H37N7O3S [ No CAS ]
YieldReaction ConditionsOperation in experiment
Example 81 :W-[(3S)-1-acryloyl-3-pyrrolidinyl]-4-[(2(2-dimethyl-4-morpholiny.)methyl]-W'- [1 ,3]thiazolo[5,4-i)3pyridin-2-yl-2,6-pyridinediamineA solution of 1 ,1 -dimethyiethyl (3S)-3-[4-formyl-6-([1 ,3]thiazo.o[5,4-/b]pyridin-2-ylamino)- 2-pyridinyi]amino}-1-pyrrolidinecarboxy.ate (50 mg, 0.114 mmol) in tetrahydrofuran (0.5 mL) was treated with <strong>[147688-58-2]2,2-<strong>[147688-58-2]dimethylmorpholine</strong></strong> (26.1 mg, 0.227 mmol) and the reaction mixture was stirred for 15 minutes. The mixture was then treated with dichloromethane (2 mL) and sodium triacetoxyborohydride (48.1 mg, 0.227 mmol). The reaction mixture was stirred for 16 hours. Saturated aqueous sodium bicarbonate (1 mL) was added and the reaction was stirred for 30 minutes. Dichloromethane (5 mL) was added and the phases were separated. The organic extract was dried using a hydrophobic frit and evaporated to dryness. A round bottom flask was charged with the obtained solid, 4M HCI in dioxane (1.186 mL, 4.74 mmol), dichloromethane (3 mL) and methanol (2 mL). The reaction was stirred at room temperature for 1 hour. A further portion of 4M HCI in dioxane (1.186 mL, 4.74 mmol) was added and the reaction was stirred for 30 minutes. The solvent was evaporated to dryness. The residue was dissolved in W-methyl-2-pyrrolidone (1 mL) and treated with V,/V-diisopropylethy.amine (0.104 mL, 0.593 mmol) and 2-propenoyl chloride (0.019 mL, 0.237 mmol). The reaction was stirred at room temperature for 1 hour. The mixture was subjected to purification by mass directed automated preparative HPLC (ammonium bicarbonate modifier) to afford the title compound (27 mg, 0.055 mmol, 48 % yield) as a light brown solid. LCMS (Method D): Rt 0.95 minutes; m/ 494 (MH+).
  • 23
  • [ 147688-58-2 ]
  • [ 179321-49-4 ]
  • [ 1378034-63-9 ]
YieldReaction ConditionsOperation in experiment
97% With sodium tris(acetoxy)borohydride; In dichloromethane; at 25℃; for 6h; To a solution of tert-butyl 4-oxocyclohexylcarbamate (350 mg, 1.641 mmol) in methylene chloride (8 mL) was added <strong>[147688-58-2]2,2-<strong>[147688-58-2]dimethylmorpholine</strong></strong> (189 mg, 1.641 mmol) followed by sodium triacetoxyborohydride (1.739 g, 8.21 mmol). Reaction mixture was stirred at 25 C for 6 hr. Reaction mixture was diluted with EtOAc and washed with water. Organics were isolated, dried (MgS04), filtered and concentrated under reduced pressure. The residue was purified by column chromatography [Si02; 12 g] to provide the title compound as a yellow oil. LCMS (m/z): 313.1 [M+H]+; Retention time = 0.60 min.
With sodium tris(acetoxy)borohydride; In dichloromethane; at 25℃; for 6h; To a solution of tert-butyl 4-oxocyclohexylcarbamate (350 mg, 1.641 mmol) in methylene chloride (8 mL) was added <strong>[147688-58-2]2,2-<strong>[147688-58-2]dimethylmorpholine</strong></strong> (189 mg, 1.641 mmol) followed by sodium triacetoxyborohydride (1.739 g, 8.21 mmol). Reaction mixture was stirred at 25 C for 6 hr. Reaction mixture was diluted with EtOAc and washed with water. Organics were isolated, dried (MgS04), filtered and concentrated under reduced pressure. The residue was purified by column chromatography [Si02; 12 g] to provide the title compound as a yellow oil. LCMS (m/z): 313.1 [M+H]+; Retention time = 0.60 min
With sodium tris(acetoxy)borohydride; In dichloromethane; at 25℃; for 6h; To a solution of tert-butyl 4-oxocyclohexylcarbamate (350 mg, 1.641 mmol) in methylene chloride (8 mL) was added <strong>[147688-58-2]2,2-<strong>[147688-58-2]dimethylmorpholine</strong></strong> (189 mg, 1.641 mmol) followed by sodium triacetoxyborohydride (1.739 g, 8.21 mmol). Reaction mixture was stirred at 25 C for 6 hr. Reaction mixture was diluted with EtOAc and washed with water.Organics were isolated, dried (MgS04), filtered and concentrated under reduced pressure. The residue was purified by column chromatography [Si02; 12 g] to provide the title compound as a yellow oil. LCMS (m/z): 313.1 [M+H]+; Retention time = 0.60 min
With sodium tris(acetoxy)borohydride; In dichloromethane; at 25℃; for 6h; Synthesis of cis- and frans-4-(2,2-dimethylmorpholino)cyclohexanamineStepl : Preparation of tert-butyl cis/trans-4-(2,2-dimethylmorpholino)cyclohexylcarbamateTo a solution of tert-butyl 4-oxocyclohexylcarbamate (350 mg, 1.641 mmol) in methylene chloride (8 mL) was added <strong>[147688-58-2]2,2-<strong>[147688-58-2]dimethylmorpholine</strong></strong> (189 mg, 1.641 mmol) followed by sodium triacetoxyborohydride (1.739 g, 8.21 mmol). Reaction mixture was stirred at 25 C for 6 hr. Reaction mixture was diluted with EtOAc and washed with water.Organics were isolated, dried (MgS04), filtered and concentrated under reduced pressure. The residue was purified by column chromatography [Si02; 12 g] to provide the title compound as a yellow oil. LCMS (m/z): 313.1 [M+H]+; Retention time = 0.60 min.

  • 24
  • [ 147688-58-2 ]
  • [ 179321-49-4 ]
  • [ 1341428-30-5 ]
  • 25
  • [ 147688-58-2 ]
  • [ 179321-49-4 ]
  • [ 1378034-64-0 ]
  • 26
  • [ 1382981-73-8 ]
  • [ 147688-58-2 ]
  • [ 1382981-77-2 ]
YieldReaction ConditionsOperation in experiment
85% In isopropyl methanesulfonate; at 140℃; for 0.333333h;Microwave irradiation; Step 1 : 3-Chloro-l-(2,2-dimethyl-morpholin-4-yl)-8,8-dimethyl-5,6-dihydro-8H- 7-oxa-2,4,4b,9-tetraaza-fluoreneA mixture of l,3-dichloro-8,8-dimethyl-5,6-dihydro-8H-7-oxa-2,4,4b,9-tetraaza-fluorene (100 mg, 0.366 mmol), <strong>[147688-58-2]2,2-<strong>[147688-58-2]dimethyl-morpholine</strong></strong> (84 mg, 0.732 mmol) and triethylamine (77 mu, 0.55 mmol) in IMS (2 mL) was heated at 140 C for 20 mins in a microwave reactor, then concentrated in vacuo. The resulting residue was purified by column chromatography (Si02, 10% ethyl acetate in cyclohexane) affording 3-Chloro-l-(2,2-dimethyl-morpholin-4-yl)-8,8- dimethyl-5,6-dihydro-8H-7-oxa-2,4,4b,9-tetraaza-fluorene as a white solid (110 mg, 85%).LCMS (method A): RT = 3.51 min, [M+H]+ = 352.
  • 27
  • [ 147688-58-2 ]
  • [ 179321-49-4 ]
  • 4-(2,2-dimethylmorpholino)cyclohexanamine trifluoroacetate [ No CAS ]
  • 28
  • [ 10397-13-4 ]
  • [ 147688-58-2 ]
  • 4-(6-chloro-2-morpholinopyrimidin-4-yl)-2,2-dimethylmorpholine [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In ethanol; at 110℃; for 0.416667h;Microwave irradiation; Step 1: A mixture of <strong>[147688-58-2]2,2-<strong>[147688-58-2]dimethylmorpholine</strong></strong> (2.0 equiv.), 4-(4,6-dichloropyrimidin-2-yl)morpholine (1 equiv.) and triethylamine (6 equiv.) in EtOH (0.2 M) were heated to 110 C. for 25 min in the microwave. The reaction mixture was partitioned between EtOAc and water. The organic phase was dried over sodium sulfate. The resulting solution was concentrated and dried under vacuo to give 4-(6-chloro-2-morpholinopyrimidin-4-yl)-<strong>[147688-58-2]2,2-<strong>[147688-58-2]dimethylmorpholine</strong></strong> and was used in the next step without further purification. LCMS (m/z) (M+H)=313.2, Rt=0.86 min.
  • 29
  • [ 10397-13-4 ]
  • [ 147688-58-2 ]
  • N-(3-(6-(2,2-dimethylmorpholino)-2-morpholinopyrimidin-4-yl)-4-methylphenyl)-3-(trifluoromethyl)benzamide [ No CAS ]
  • 30
  • [ 147688-58-2 ]
  • [ 138500-85-3 ]
  • 2,2-dimethyl-4-[[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]methyl]morpholine [ No CAS ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; at 20℃; for 22h;Inert atmosphere; To a stirred solution of 2-[4-(bromomethyl)phenyl]-4,4,5,5-tetramethyl-1 ,3,2-dioxaborolane (300.0 mg, 1 .01 mmol) and Lambda/,/V-diisopropylethylamine (0.36 mL, 2.02 mmol) in THF (5.0 mL) under nitrogen was added <strong>[147688-58-2]2,2-<strong>[147688-58-2]dimethylmorpholine</strong></strong> (139.6 mg, 1 .21 mmol), and the reaction was stirred at room temperature for 22 h. The reaction mixture was concentrated under reduced pressure to give 2,2- dimethyl-4-[[4-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)phenyl]methyl]morpholine (334.6 mg, 1 .01 mmol, 100% yield) as a mixture with Lambda/,/V-diisopropylethylamine. This mixture was used in the next reaction without further purification, assumed quantitative. UPLC-MS (ES+, Short acidic): 1 .32 min, m/z 332.0 [M+H]+
  • 31
  • [ 1215865-85-2 ]
  • [ 147688-58-2 ]
  • (S)-2'-(2,2-dimethylmorpholino)-7'-(pyrimidin-5-yl)-5H-spiro[oxazole-4,9'-xanthen]-2-amine [ No CAS ]
  • 32
  • (4S)-7-chloro-2,3,4,5-tetrahydro-1,4-methanopyrido[2,3-b] [1,4]diazepine [ No CAS ]
  • [ 147688-58-2 ]
  • 2,2-dimethyl-4-((4S)-2,3,4,5-tetrahydro-1,4-methanopyrido[2,3-b][1,4]diazepin-7-yl)morpholine [ No CAS ]
YieldReaction ConditionsOperation in experiment
52.3% With (1,3-bis(2,6-diisopropylphenyl)-4,5-dihydroimidazol-2-ylidene)chloro(3-phenylallyl)palladium(II); potassium tert-butylate; In 1,2-dimethoxyethane; at 90℃; for 16h;Inert atmosphere; A suspension of (4S)-7-chloro-2,3,4,5-tetrahydro-1,4-methanopyrido[2,3-b][1,4]diazepine (1.0 g, 5.11 mmol), <strong>[147688-58-2]2,2-<strong>[147688-58-2]dimethylmorpholine</strong></strong> (1.177 g, 10.22 mmol) and KOtBu (1.147 g, 10.22 mmol) in 1,2-Dimethoxyethane (DME) (20 mL) was stirred and degassed with argon at room temp for 15 mins. Then (1,3-Bis(2,6-di-isopropylphenyl)-4,5-dihydroimidazol-2-ylidene)chloro) (3-phenylallyl)palladium(2) (0.133 g, 0.204 mmol) was added to the reaction mixture. The reaction mixture was stirred 16 hr at 90 C. The reaction mass was filtered through celite and the solvent evaporated. The reaction mixture was diluted with EtOAc and washed with water followed by brine solution. The solution was dried over sodium sulfate, filtered and evaporated to give the crude product. The crude product was added to a neutral alumina column and was eluted with DCM to afford 2,2-dimethyl-4-((4S)-2,3,4,5-tetrahydro-1,4-methanopyrido[2,3-b][1,4]diazepin-7-yl)morpholine (0.800 g, 2.67 mmol, 52.3% yield) as a white solid, LCMS (m/z) 275.0 [M+H]+.
52.3% A suspension of (4S)-7-chloro-2,3,4,5-tetrahydro-l,4-methanopyrido[2,3-b][l,4]diazepine (1.0 g, 5.11 mmol), <strong>[147688-58-2]2,2-<strong>[147688-58-2]dimethylmorpholine</strong></strong> (1.177 g, 10.22 mmol) and KOtBu (1.147 g, 10.22 mmol) in 1,2-Dimethoxy ethane (DME) (20 mL) was stirred and degassed with argon at room temp for 15 mins. Then (l,3-Bis(2,6-di-isopropylphenyl)-4,5- dihydroimidazol-2-ylidene)chloro) (3-phenylallyl)palladium(2) (0.133 g, 0.204 mmol) was added to the reaction mixture. The reaction mixture was stirred 16 hr at 90 C. The reaction mass was filtered through celite and the solvent evaporated. The reaction mixture was diluted with EtOAc and washed with water followed by brine solution. The solution was dried over sodium sulfate, filtered and evaporated to give the crude product. The crude product was added to a neutral alumina column and was eluted with DCM to afford 2,2-dimethyl-4-((4S)-2,3,4,5-tetrahydro-l,4-methanopyrido[2,3-b][l,4]diazepin-7- yl)morpholine (0.800 g, 2.67 mmol, 52.3 % yield) as a white solid, LCMS (m/z) 275.0 [M+H]+.
  • 33
  • 1-(4-fluorophenyl)-6-formyl-4-oxo-1,4-dihydroquinoline-3-carboxamide [ No CAS ]
  • [ 147688-58-2 ]
  • 6-((2,2-dimethylmorpholino)methyl)-1-(4-fluorophenyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide [ No CAS ]
  • 34
  • 4-chloro-7-(2-fluorobenzenesulfonyl)-2-methyl-5H-pyrrolo[3,2-d]pyrimidin-6-amine [ No CAS ]
  • [ 147688-58-2 ]
  • 4-(2,2-dimethylmorpholin-4-yl)-7-(2-fluorobenzenesulfonyl)-2-methyl-5H-pyrrolo[3,2-d]pyrimidin-6-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In ethanol; at 140℃; for 3h;Microwave irradiation; Example 5a: 7-(henzenesnhfonyl)-4-(2-methyhnorpholin-4-yl)-5H- pyrrolo[, 2-d]pyrimidin-6-amine To a stirred solution of 7-(benzenesulfonyl)-4-chloro-5H-pyrrolo[3,2-djpynmidin-6- amine (Intermediate 3; 200 mg, 648 pmol), 2-methylmorpholine (CM 27550-90-9; 262 mg, 2.59 mmol) and triethylamine (i8i iL, 1.30 mmol) in anhydrous DMF (8 mL) and the reaction mixture was heated under microwave irradiation at 130 C for 2 b. The reaction mixture poured into water and extracted with EtOAc. The combined organic fractions were washed with brine and concentrated in vacuo. The crude product was purified by column chromatography (preparative HPLC, 5-40% acetonitrile / water (with o.i% ammonia)) to afford the title compound.ifl Example 185: 4-(2,2-dlmcthylmorpholin-4-yI)-7-(2- fluorobenzenesulfonyfl-2-methyl-5H-pyrrolo[3 ,2-d]pyrhnidin-6-ainine Prepared as described for 7-(benzenesulfonyl)-4--(2-methylmorpholin-4-yl)5H- pyrrolo[3,2-djpyrimidin-6-amine (Exampk 52) from 4-chloro-7-(2- fluorobenzenesulfonyl)-2-methyk5H-pyrrolo[3,2-djpyrimidin-6-amine (Intermediate o; 250 mg, 734 jamol) and 2,2-dimethymorpho1ine (CM 147688-58-2; 127 mg, 1.1 mmol) in EtOH (6 mL) and the reaction mixture was heated under microwave irradiation at 140 C for h. The crude product was purified by column chromatography (preparative HPLC, 20-60% acetonitrile / water (with oa% ammonia)) and recrystallised from chloroform / petroleum ether to afford the title compound.?H NMR (400 MHz, DMSO-d6 + TFA-d) 6 ppm 1.18 (s, 6 H) 2.60 (s, 3 H) 3.59 - 3.90 (m, 6 H) 7.34 - 7.53 (m, 2 H) 7.74 (m, 1 H) 8.o6 - 8.23 (m, iH).MS ESi 420
  • 35
  • [ 13162-43-1 ]
  • [ 147688-58-2 ]
  • 4-(6-chloro-2-methyl-5-nitropyrimidin-4-yl)-2,2-dimethylmorpholine [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In dichloromethane; at 0 - 25℃; for 2h; Intermediate 112: 4-(6-CJIIorO-2-methyl-5-flitropyrinhidin-4-yl)-2,2- dimethylmorpholine To a stirred solution of 4,6-diehloro-2-methyl-5-nitropyrimidine (CM 13162-43-1; 10 g, 48.1 mmol) and triethylamine (c7? mL, 52.9 mmol) in DCM (9 mL) at o C was added a solution of 2,2-dimethylmorpholine (CM 147688-58-2; 5.54 g, 48.1 mmol) in DCM (30 mIj. The reaction mixture was allowed to warm to it and stirred for 2 h. The reaction mixture was concentrated in vacuo. The resulting residue was dissolved in ethyl acetate and washed with water, io% aq. citric acid solution, sat. aq. NaHCO3 solution and brine. The organics were separated, dried (MgSO4) and concentrated invacuo to afford the flUe compound.1H NMR (400 MHz, DM50-cl6) 6 ppm i.i6 (s, 6 H) 2.46 (s, 3 H) 3.27 - 3.34 (m, 211)3.51 (s, 2 H) 3.68 - 3.72 (m, 2 H)MS ES: 287
  • 36
  • [ 13162-43-1 ]
  • [ 147688-58-2 ]
  • 2-(2,4-difluorobenzenesulfonyl)-2-[6-(2,2-dimethylmorpholin-4-yl)-2-methyl-5-nitropyrimidin-4-yl]acetonitrile [ No CAS ]
  • 37
  • 4-chloro-7-(4-methoxybenzenesulfonyl)-2-methyl-5H-pyrrolo[3,2-d]pyrimidin-6-amine [ No CAS ]
  • [ 147688-58-2 ]
  • 4-(2,2-dimethylmorpholin-4-yl)-7-(4-methoxybenzenesulfonyl)-2-methyl-5H-pyrrolo[3,2-d]pyrimidin-6-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In ethanol; at 160℃; for 5h;Microwave irradiation; Example 204: 4-(2,2-dimethylmorpholin-4-yl)-7-(4- methoxybenzenesulfonyl)-2-methyl-5fl-pyrrolo[3 ,2-d]pyrmudin-6-an1ine To a stirred solution of 4-chloro-7-(4-methoxybenzenesulfonyl)-2-methyl-5H- pyrrolo[3,2-d]pyrimidin-6-amine (Intermediate 57; 400 mg, 1.13 mmol) and tricthylamine (316 jiL, 2.27 mmol) in EtOH (io mL) was added 2,2- <strong>[147688-58-2]dimethylmorpholine</strong> (CM 147688-58-2; 196 mg, 1.70 mmol) and the reaction mixture was heated under microwave irradiation at i6o C for h. The reaction mixture was concentrated in vacuo and partitioned between EtOAc and water. The organic phase was dried (H-fit). The crude product was purified by column chromatography (silica, o-ioo% EtOAc / petroleum ether) and recrystallised from EtOH / water to afford the title compound. ?H NMR (400 MHz, DMSO-d6 ÷TFA-d) 6 ppm i.i6 (s, 6 H) 2.63 (s, 3 H) 3.68 (s, 2 H)3.71 - 3.81 (m, 4 H) 3.83 (s, 3 H) 7.13 (d, J=9 Hz, 2 H) 8.12 (d, J=9 Hz, 2 H)MS ES: 432
  • 38
  • 4-chloro-7-(2-fluoro-4-methoxybenzenesulfonyl)-2-methyl-5H-pyrrolo[3,2-d]pyrimidin-6-amine [ No CAS ]
  • [ 147688-58-2 ]
  • 4-(2,2-dimethylmorpholin-4-yl)-7-(2-fluoro-4-methoxybenzenesulfonyl)-2-methyl-5H-pyrrolo[3,2-d]pyrimidin-6-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In ethanol; at 155℃; for 3h;Microwave irradiation; Example 241: 4-(2,2-dilnethylinorpholin-4-yl)-7-(2-fluoro-4- methoxybcnzenesulfonyl)-2-methyl-5H-pyrrolo [3,a-d]pyriuildin-6-amine A solution of 4-chloro-7-(2-fluoro-4-methoxybenzenesulfonyl)-2-methyl-5H- pyrrolo[3,2-d]pyrimidin-6-amine (Intermediate 69; 50 mg, 135 iimol), 2,2- dimethymorpho1ine (31.1 mg, 270 iimol), triethylamine (6 jiL, 405 amol) and EtOH (1.5 ml,) was heated under microwave irradiation at 155 C for h. The reaction mixture was concentrated in vacua and the resulting residue diluted with water, acidiefied (pH 4) with % aq. citric acid solution and extracted with EtOAc. The combined organics were washed with brine, dried (H-fit) and concentrated in vacuo. The crude product was purified by column chromatography (preparative HPLC, 20- 6o% acetonitrile / water (with oa% ammonia)) to afford the title compound. ?H NMR (400 MHz, DMSO-d6 + TFA-d) 6 ppm 1.19 (s, 6 H) 2.61 (s, 3 H) 3.70 (s, 2 H) 3.74 - 3.83 (m, 4 H) 3.85 (s, 3 H) 6.97- 7.02 (m, 1 H) 7.03 - 7.09 (m, 1 H) 7.14 -7.28 (m, 1 H) 8.o6 - 8.12 (m, 1 H)MS ES: 450
  • 39
  • 3,5-dichloro-N-[(4-methoxyphenyl)methyl]pyridazin-4-amine [ No CAS ]
  • [ 147688-58-2 ]
  • 5-chloro-3-(2,2-dimethylmorpholin-4-yl)-N-[(4-methoxyphenyl)methyl]pyridazin-4-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine; In dimethyl sulfoxide; at 180℃; for 2h;Microwave irradiation; Intermediate 71: 5-chJoro-3-(2,2-dilnethyhnorpholin-4-yI)-N- [- mcthoxyphenyl)mcthyl]pyridazin-4-aininc To a stirred solution of 3,5-dichloro-N-(4-methoxybenzyl)pyridazin-4-amine (6o mg, 2.288 mmol) in DM80 (8 mL) was added ethylbis(propan-2-yflamine (0.799 mL, 4.58 mmol) and 2,2-dimethylmorph6line (CM 147688-58-2; 790 mg, 6.86 mmofl. The reaction mixture was heated under microwave irradiation at 18o C for 2 h. The reaction mixture was poured into water and extracted with EtOAc. The combined organics were dried (MgSO4) and concentrated in vacuo. The crude product was purified by column chromatography (silica, o-ioo% EtOAc / petroleum ether) to afford the title compound.1H NMR (400 MHz, DMSO-d6) 6 ppm 1.20 - 1.28 (m, 6 H) 2.85 - 3.03 (m, 4 H) 3.70 (s,3 H) 3.80 - 3.90 (m, 2 H) 4.63 - 4.77 (m, 2 H) 6.12 - 6.21 (m, 1 H) 6.79 - 6.89 (m, 2 14)7.12 - 7.23 (m, 2 H) 8.52 (s, 1 H)MS ESi 363
  • 40
  • 2-(6-chloro-2-methyl-5-nitropyrimidin-4-yl)-2-(2,6-difluorobenzenesulfonyl)acetonitrile [ No CAS ]
  • [ 147688-58-2 ]
  • 2-(2,6-difluorobenzenesulfonyl)-2-[6-(2,2-dimethylmorpholin-4-yl)-2-methyl-5-nitropyrimidin-4-yl]acetonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; In tetrahydrofuran; at 60℃; for 72h;Inert atmosphere; Intermediate 124: 2-(2,6-dffluorobenzenesulfonyl)-2-[6-(2,2- dimethylmorpholin-4-yl)-2-methyl-5-nitropyrinlidin-4-yl]acetonitrile A stirred solution of 2-(6-chloro-2-methyl-5-rntropyflmidin-4-yl)-2-((2,6- difluorophenyl)sulfonyl)aeetonitrile (Intermediate i 86i mg, i.86i mmol), 2,2- <strong>[147688-58-2]dimethylmorpholine</strong> (257 mg, 2.233 mmol) and K2C03 (771 mg, 5.58 mmol) in THF (20 mE) under under an atmosphere of nitrogen was heated to 6oC for 72 h. The reaction mixture was concentrated in vacuo and the residue partitioned between sat. aq. NH4C1 solution and EtOAc. The aqueous phase was extracted with EtOAc and the combined organic layers were washed with brine, dried (H-flit) and concentrated in vacuo to afford the title compound.MS ES: 468
  • 41
  • tert-butyl 4-[3-(hydroxymethyl)-5-oxo-4,5-dihydropyrazolo[1,5-a]pyrimidin-7-yl]piperidine-1-carboxylate [ No CAS ]
  • [ 147688-58-2 ]
  • tert-butyl 4-{3-[(2,2-dimethylmorpholin-4-yl)methyl]-5-oxo-4,5-dihydropyrazolo[1,5-a]pyrimidin-7-yl}piperidine-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
61% tert-butyl 4- [3 -(hydroxymethyl)-5 -oxo-4,5 -dihydropyrazolo [ 1 ,5-a]pyrimidin-7-yl]piperidine- 1 - carboxylate (150 mg, 431 muiotaetaomicron) and Triphenylphosphine (430 mu, 1.0 M, 430 muiotaetaomicron) were dissolved in Tetrahydrofuran (5.0 ml, 62 mmol) and cooled to -18 C. N-Bromsuccinimide (76.6 mg, 431 muiotaetaomicron) was added and the mixture was stirred for 5 min at -18 C. <strong>[147688-58-2]2,2-<strong>[147688-58-2]dimethylmorpholine</strong></strong> (119 mg, 1.03 mmol) was added and stirred for 10 min at RT and then for 1 h at 80 C. Water was added and purified by preparative HPLC (Method: column: Reprosil C18; 10 muiotaeta; 125x30 mm / flow: 50 ml/min / solvents: A = water (0,01% formic acid), B = acetonitrile / gradient: : 0.00-5.00 min = 10%B, 6.50min = 20%B, 17.0-19.75min = 100%B, 19.75.00-23.00min = 90%B). Evaporation of the combined product fractions yielded the title compound (118 mg, 99 % purity, 61 % of theory). LC-MS (Method 11B): Rt = 1.02 min; MS (ESIpos): m z = 446 [M+H]+
  • 42
  • [ 147688-58-2 ]
  • [ 1283761-17-0 ]
  • 43
  • [ 147688-58-2 ]
  • [ 1245465-94-4 ]
  • 44
  • [ 147688-58-2 ]
  • [ 1245463-95-9 ]
  • 45
  • [ 147688-58-2 ]
  • [ 1245464-32-7 ]
  • 46
  • 6-(4-bromophenyl)-3-((2-chlorophenyl)thio)-4-hydroxy-6-(thiophen-3-yl)-5,6-dihydropyridin-2(1H )-one [ No CAS ]
  • [ 147688-58-2 ]
  • 3-(2-chlorophenyl)sulfanyl-6-[4-(2,2-dimethylmorpholin-4-yl)pheny1]-6-(3-thienyl)piperidine-2,4-dione [ No CAS ]
  • 47
  • 4-(4-fluorophenyl)-5-formylpicolinonitrile [ No CAS ]
  • [ 147688-58-2 ]
  • 5-((2,2-dimethylmorpholino)methyl)-4-(4-fluorophenyl)picolinonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
36% Compound L (prepared according to Example 2) (15 mg, 0.066 mmol, 1.0 eq) was dissolved in dichloromethane (0.5 mL) and <strong>[147688-58-2]2,2-<strong>[147688-58-2]dimethylmorpholine</strong></strong> (T) (15 mg, 0.13 mmol, 2.0 eq) and acetic acid (9.5 tL, 0.17 mmol, 2.5 eq) were added. The reaction was stirred for one hour, and sodium triacetoxyborohydride (21 mg, 0.10 mmol, 1.5 eq) was added. After stirring for an additional hour, the reaction was concentrated and purified by reverse-phase HPLC to afford 7.8 mg (36%) of the title compound as white solid. ?H NIVIR (400 IVIFIz, DMSO-d6) 8.80 (s, 1H), 8.00 (s, 1H), 7.66-7.62 (m, 2H), 7.37-732 (m, 2H), 3.51 (t, J = 4.7 Hz, 2H), 3.46 (s, 2H), 2.20 (m, 2H), 2.05 (s, 2H), 1.06 (s, 6H); ES-MS [M+1]: 326.3.
  • 48
  • 3-bromo-7-(4-methoxybenzyl)-6-methylimidazo[1,5-a]pyrazin-8(7H)-one [ No CAS ]
  • [ 147688-58-2 ]
  • 3-(2,2-dimethylmorpholino)-7-(4-methoxybenzyl)-6-methylimidazo[1,5-a]pyrazin-8(7H)-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
3% With potassium carbonate; cesium fluoride; In dimethyl sulfoxide; at 100℃; for 24h; To a mixture of 3-bromo-7-(4-methoxybenzyl)-6-methyl imidazo[1 ,5-a]pyrazin-8(7H)-one (500 mg, 1 .44 mmol) and <strong>[147688-58-2]2,2-<strong>[147688-58-2]dimethylmorpholine</strong></strong> (331 mg, 2.88 mmol) in DMSO (5 mL) wereadded CsF (328 mg, 2.88 mmol) and K2003 (299 mg, 2.88 mmol). The mixture was stirred at100C for 24 hours. The mixture was diluted with water (20 mL) and extracted with DCM (10 mL x 3). The combined organic layer was washed with water (10 mL x 2); dried over Na2SO4 and evaporated under vacuum. The residue was purified by preparative TLC (ethyl acetate) to give 3-(2,2-dimethylmorpholino)-7-(4-methoxybenzyl)-6-methylimidazo[1 ,5-a]pyrazin-8(7H)-one (15 mg, 3% yield).1H NMR (ODd3, 400 MHz): 7.75 (s, 1H), 7.15 (d, J= 8.8 Hz, 2H), 6.85 (d, J= 8.8 Hz, 2H),6.60 (s, 1 H), 5.15 (s, 2H), 3.93 (t, J = 4.8 Hz, 2H), 3.79 (s, 3H), 3.16 (t, J = 4.8 Hz, 2H), 2.98(s, 2H), 2.18 (s, 3H), 1.37 (s, 6H).LC-MS: tR = 2.26 mm (method 13), m/z = 383.1 [M + H] .
3% With potassium carbonate; cesium fluoride; In dimethyl sulfoxide; at 100℃; for 24h; To a mixture of 3-bromo-7-(4-methoxybenzyl)-6-methylimidazo[1 ,5-a]pyrazin-8(7H)-one (500 mg, 1.44 mmol) and <strong>[147688-58-2]2,2-<strong>[147688-58-2]dimethylmorpholine</strong></strong> (331 mg, 2.88 mmol) in DMSO (5 mL) were added CsF (328 mg, 2.88 mmol) and K2CO3 (299 mg, 2.88 mmol). The mixture was stirred at 100C for 24 hours. The mixture was diluted with water (20 ml_) and extracted with DCM (10 ml_ x 3). The combined organic layer was washed with water (10 ml_ * 2); dried over Na2S04 and evaporated under vacuum. The residue was purified by preparative TLC (ethyl acetate) to give 3-(2,2-dimethylmorpholino)-7-(4-methoxybenzyl)-6-methylimidazo[1 ,5-a]pyrazin- 8(7H)-one (15 mg, 3% yield). 1H NMR (CDCl3 , 400 MHz): delta 7.75 (s, 1 H), 7.15 (d, J = 8.8 Hz, 2H), 6.85 (d, = 8.8 Hz, 2H), 6.60 (s, 1 H), 5.15 (s, 2H), 3.93 (t, J = 4.8 Hz, 2H), 3.79 (s, 3H), 3.16 (t, J = 4.8 Hz, 2H), 2.98 (s, 2H), 2.18 (s, 3H), 1.37 (s, 6H). LC-MS: tR = 2.26 min (method 13), m/z = 383.1 [M + H] +.
3% With potassium carbonate; cesium fluoride; In dimethyl sulfoxide; at 100℃; for 24h; To a mixture of 3-bromo-7-(4-methoxybenzyl)-6-methylimidazo[1 ,5-a]pyrazin-8(7H)-one (500 mg, 1.44 mmol) and <strong>[147688-58-2]2,2-<strong>[147688-58-2]dimethylmorpholine</strong></strong> (331 mg, 2.88 mmol) in DMSO (5 ml_) were added CsF (328 mg, 2.88 mmol) and K2C03 (299 mg, 2.88 mmol). The mixture was stirred at 100C for 24 hours. The mixture was diluted with water (20 mL) and extracted with DCM (10 ml_ chi 3). The combined organic layer was washed with water (10 mL chi 2); dried over Na2S04 and evaporated under vacuum. The residue was purified by preparative TLC (ethyl acetate) to give 3-(2,2-dimethylmorpholino)-7-(4-methoxybenzyl)-6-methylimidazo[1 ,5-a]pyrazin- 8(7H)-one (15 mg, 3% yield). (1340) 1H NMR (CDCis, 400 MHz): delta 7.75 (s, 1 H), 7.15 (d, J = 8.8 Hz, 2H), 6.85 (d, J = 8.8 Hz, 2H), 6.60 (s, 1 H), 5.15 (s, 2H), 3.93 (t, J = 4.8 Hz, 2H), 3.79 (s, 3H), 3.16 (t, J = 4.8 Hz, 2H), 2.98 (s, 2H), 2.18 (s, 3H), 1.37 (s, 6H). (1341) LC-MS: tR = 2.26 min (method 13), m/z = 383.1 [M + H] +.
  • 49
  • [ 1197050-28-4 ]
  • [ 147688-58-2 ]
  • 4-(3-bromo-2-chlorobenzyl)-2,2-dimethylmorpholine [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sodium tris(acetoxy)borohydride; acetic acid; In dichloromethane; at 20℃; for 1h;Inert atmosphere; To a flask contanng (250 mg, 1.14 mmo) and 2,2- dmethymorphohne (157mg, 1.37 mmo) n DCM (3.8 rnL) was added acetcacd (6.5 1iL, 0.11 mmo), foHowed by sodium tracetoxyborohydrde (290 mg, 1.37 mmofl. The reacUon mixture was stirred at rt for I h, dHuted wfth water, and then extracted twice wfth EtOAc.The combined organic extracts were dred over Na2SO4, fl[tered, and concentrated nvacuo to provide the tWe compound as an o. 1H NMR (400 MHz, DMSO-d5) oe 7.68 (dd, J= 8.0, 1.6 Hz, I H), 7.53 (ddd, J = 7.6, 1.6, 0.8 Hz, I H), 7.28 (t, J = 7.8 Hz, I H), 3.62 (dd, J= 5.7, 4.0 Hz, 2H), 3.53 (s, 2H), 2.40 2.27 (m, 2H), 2.21 (5, 2H), 1.20 1.09 (s, 6H).
  • 50
  • 6-(2-chloropyrimidin-5-yl)-1-(2-(difluoromethoxy)benzyl)-2-methyl-1H-indazol-3(2H)-one [ No CAS ]
  • [ 147688-58-2 ]
  • 1-(2-(difluoromethoxy)benzyl)-6-(2-(2,2-dimethylmorpholino)pyrimidin-5-yl)-2-methyl-1H-indazol-3(2H)-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
61% With triethylamine; In ethanol; at 80℃; for 20h; Example 2: l-(2-(Difluoromethox )benzyl)-6-(2-(2,2-dimethylmorpholino)p rimidin-5-yl)-2- methyl-lH-indazol-3(2H)-one A flask was charged with 6-(2-chloropyrimidin-5-yl)- l-(2-(difluoromethoxy)benzyl)-2-methyl-lH- indazol-3(2H)-one (50 mg, 0.12 mmol) (Preparation 4), <strong>[147688-58-2]2,2-<strong>[147688-58-2]dimethylmorpholine</strong></strong> (28 mg, 0.24 mmol), EtOH (1.5 mL) and TEA (0.033 mL, 0.24 mmol). The reaction mixture was heated at about 80 C for about 20 h. The reaction mixture was cooled to rt and then purified via reverse phase HPLC (Table 1, Method g) to give the title product (36 mg, 61 %); LC/MS (Table A, Method a) Rt = 2.31 min; MS m/z: 496 (M+H)+ (TNF 1C50 = A).
  • 51
  • 3-(3'-fluoro-4'-methylphenyl)benzoic acid [ No CAS ]
  • [ 147688-58-2 ]
  • (2,2-dimethylmorpholino)(3'-fluoro-4'-methyl-[1,1'-biphenyl]-3-yl)methanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
88% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; acetonitrile; for 1.2h; To a suspension of 178 mg 3-(3'-fluoro-4'-methylphenyl)-benzoic acid (0.76 mmol) in 7 mL of a 6:1 DCM/MeCN mixture in a round-bottomed flask 1 14 mg HOBt (0.83 mmol) and 161 mg EDC*HCI (0.83 mmol) were added and after complete dissolution 91 mg <strong>[147688-58-2]2,2-<strong>[147688-58-2]dimethylmorpholine</strong></strong> (0.75 mmol) were given. After stirring for 1.2 h the mixture was concentrated under reduced pressure, taken-up in AcOEt (40 mL), then washed with 5 % KHSO4 (2x18 mL) and H2O (12 mL). The organic phase was concentrated under reduced pressure, taken-up in 4 mL of an 1:1 MeOH/H2O mixture and 42 mg LiOH*H2O (1.0 mmol) were added, then the mixture was stirred at 50C to hydrolyze the unreacted active ester. After 1 h the mixture was cooled to room temperature, diluted with AcOEt (30 mL), washed with 5 % Na2CO3 (5x15 mL) and brine (15 mL), dried over Na2SO4, filtered and evaporated to dryness under reduced pressure. 219 mg product lll-a were obtained (88 % yield). LR-MS: m/z 328.2 ([M+H]+, clc 328.17).
  • 52
  • (2E)-N-(4-formylphenyl)-3-(4-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)acrylamide [ No CAS ]
  • [ 147688-58-2 ]
  • (2E)-N-(4-((2,2-dimethylmorpholin-4-yl)methyl)phenyl)-3-(4-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)acrylamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
57 mg With 2-picoline borane complex; acetic acid; In methanol; at 10 - 35℃; for 16h; To a mixture of <strong>[147688-58-2]2,2-<strong>[147688-58-2]dimethylmorpholine</strong></strong> (42 mg), (2E)-N-(4-formylphenyl)-3-(4-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)acrylamide (60 mg), methanol (2 mL) and acetic acid (0.2 mL), 2-picoline-boron complex (29 mg) was added at room temperature, and the resulting mixture was stirred at the same temperature for 16 hours. Water was added to the reaction mixture, the mixture was concentrated under reduced pressure, and the residue was then extracted with ethyl acetate. The organic layer was washed with brine and then dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (NH, ethyl acetate/hexane) to obtain the title compound (57 mg). 1H NMR (300 MHz, DMSO-d6) delta 1.09-1.17 (6H, m), 2.11 (2H, s), 2.29 (2H, d, J=4.7 Hz), 3.38 (2H, s), 3.61 (2H, t, J=4.6 Hz), 3.93 (3H, s), 6.85 (1H, d, J=15.6 Hz), 7.27 (2H, d, J=8.3 Hz), 7.49 (1H, d, J=5.1 Hz), 7.62-7.77 (4H, m), 8.09 (1H, s), 8.53 (1H, d, J=5.3 Hz), 8.78 (1H, s), 10.28 (1H, s).
57 mg With acetic acid; In methanol; at 20℃; for 16h; At room temperature,In <strong>[147688-58-2]2,2-<strong>[147688-58-2]dimethylmorpholine</strong></strong> (42 mg),(2E) -N- (4-methylphenylphenyl) -3- (4-(1-methyl-1H-pyrazol-4-yl) pyridin-3-yl)Acrylamide (60 mg),Methanol (2 mL) and acetic acid (0.2 mL)Add to2-methylpyridine-boron complex(29 mg),The reaction mixture was stirred at the same temperature for 16 hours.Water was added to the reaction mixture, and the mixture was concentrated under reduced pressure,The residue was extracted with ethyl acetate.The organic layer was washed with brine, dried over anhydrous magnesium sulfate and the solvent was removed by distillation under reduced pressure.The residue was purified by silica gel column chromatography (NH, ethyl acetate / hexane) to give the title compound (57 mg).
  • 53
  • (6-chloro-2-methyl-5-nitro-2,3-dihydrobenzofuran-2-yl)methanol [ No CAS ]
  • [ 147688-58-2 ]
  • (6-(2,2-dimethylmorpholino)-2-methyl-5-nitro-2,3-dihydrobenzofuran-2-yl)methanol [ No CAS ]
YieldReaction ConditionsOperation in experiment
55% at 100℃; for 18h;Sealed tube; A mixture of (6-chloro-2-methyl-5-nitro-2,3-dihydrobenzofuran-2-yl)methanol (Intermediate 2) (130 mg, 0.53 mmol) in <strong>[147688-58-2]2,2-<strong>[147688-58-2]dimethylmorpholine</strong></strong> (1 mL) was stirred at 100oC for 18h in a sealed tube. After cooling to room temperature and concentration under reduced pressure, the residue was purified by silica gel chromatography using ethyl acetate:petroleum ether (2:1) as eluting solvents to afford (6-(2,2-dimethylmorpholino)-2-methyl-5-nitro-2,3-dihydrobenzofuran-2- yl)methanol (95 mg, 55 %) as a yellow solid. MS (ESI): m/z = 323.2 [M+1]+
  • 54
  • 5-amino-1-[(4-formylphenyl)methyl]-N-(3-methoxyphenyl)-1H-1,2,3-triazole-4-carboxamide [ No CAS ]
  • [ 147688-58-2 ]
  • C24H30N6O3 [ No CAS ]
  • 55
  • [ 1003845-06-4 ]
  • [ 147688-58-2 ]
  • (2-(2,2-dimethylmorpholino)pyrimidin-5-yl)boronic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In ethanol; at 75℃; for 1.5h; To a mixture of 2-chloropyrimidine-5-boronic acid (32 mg, 0.2 mmol) and <strong>[147688-58-2]2,2-<strong>[147688-58-2]dimethylmorpholine</strong></strong> (24 mg, 0.21 mmol) in EtOH (2 mL) was added triethylamine (0.070 mL, 0.5 mmol). The resulting mixture was stirred at 75 C for 1.5 h. Solvents were removed to give the crude (2-(2,2- dimethylmorpholino)pyrimidin-5-yl)boronic acid as a pale yellow solid. LCMS [M + H]+ 238.2. The title compound (beige solid, 36.6 mg, 60%) was prepared by a procedure similar to the last step of Example 31 using this boronic acid (0.2 mmol) and (S)-N-(5-bromo-2-(3,4-dimethylpiperazin-l-yl)-4-fluorophenyl)-6-oxo-4- (trifluoromethyl)-l,6-dihydropyridine-3-carboxamide (49.1 mg, 0.1 mmol). NMR (500MHz, CHLOROFORM-d) delta = 8.70 (s, 1H), 8.54 (s, 2H), 8.45 (br d, J=8.1 Hz, 1H), 7.88 (s, 1H), 7.04 (d, J=l l . l Hz, 1H), 7.00 (br s, 1H), 3.89 - 3.80 (m, 4H), 3.71 (s, 2H), 3.02 - 2.87 (m, 3H), 2.82 (br d, J=10.9 Hz, 1H), 2.86 - 2.77 (m, 1H), 2.60 (br t, J=10.4 Hz, 1H), 2.42 - 2.30 (m, 4H), 2.23 (br s, 1H), 1.28 (s, 6H), 1.10 (br d, J=6.1 Hz, 3H); LCMS [M + H]+ 604.5.
  • 56
  • [ 4175-77-3 ]
  • [ 147688-58-2 ]
  • C9H13BrN2OS [ No CAS ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 80℃;Inert atmosphere; General procedure: To a stuffed solution of 2,4-dibromothiazole (2) (4 mmol) in dimethylformamide (DMF) (15 mL), the coffesponding amine (1) (4 mmol) and diisopropylethylamine (DIPEA) (1.55 g, 2 mL, 12 mmol) were added under a stream of nitrogen.The reaction mixture was stirred at 80C for 4-10 h (monitored by Thin-layer chromatography (TLC)), then cooled to room temperature (rt), quenched with cold water (H20) (50 mL) and extracted with ethyl acetate (EtOAc) (3x30 mL). The combined organic layer was washed with H20 (2x10 mL), dried over sodium sulfate and concentrated to give the crude compound 3. The resulting product 3, the corresponding imidazole 4 (12 mmol),palladium(II)bis(triphenylphosphine) diacetate (Pd(OAc)2(PPh3)2) (0.1 mmol) and toluene (50 mL) were refluxed for 24 h. After cooling, the organic solvent was removed under vacuum. The resulting residue was purified by preparative high-performance liquid chromatography (HPLC) (EtOAc - Hexane (1:5) as eluent) to give the final product 5 as a solid. It was additionally purified by reverse phase HPLC (gradient acetonitrile (MeCN) - H20, 20 to 80% of MeCN aseluent). A compound of formula S are examples 1-15, 17-22, 24-40, 42-50 and 52-62.
  • 57
  • 3,6-di-bromo-isothiazolo[4,3-b]pyridine [ No CAS ]
  • [ 147688-58-2 ]
  • 4-(6-bromoisothiazolo[4,3-b]pyridin-3-yl)-2,2-dimethylmorpholine [ No CAS ]
  • 58
  • [ 108-77-0 ]
  • [ 147688-58-2 ]
  • 2-chloro-4,6-bis(2,2-dimethylmorpholin-4-yl)-1,3,5-triazine [ No CAS ]
  • 59
  • [ 147688-58-2 ]
  • 5-[4,6-bis(2,2-dimethylmorpholin-4-yl)-1,3,5-triazin-2-yl]-4-(difluoromethyl)-pyridin-2-amine [ No CAS ]
  • 60
  • methyl 3-({3-(4-chlorophenyl)-5-oxo-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-4,5-dihydro-1H-1,2,4-triazol-1-yl}methyl)-1-[3-(trifluoromethyl)pyridin-2-yl]-1H-1,2,4-triazole-5-carboxylate [ No CAS ]
  • [ 147688-58-2 ]
  • 5-(4-chlorophenyl)-2-({5-(2,2-dimethylmorpholine-4-carbonyl)-1-[3-(trifluoromethyl)pyridin-2-yl]-1H-1,2,4-triazol-3-yl}methyl)-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-2,4-dihydro-3H-1,2,4-triazol-3-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 40℃; for 8h;Microwave irradiation; A suspension of methyl 3-( { 3-(4-chlorophenyl)-5-oxo-4- [(2S)-3,3,3-trifluoro-2-hydroxypropyl] -4,5-dihydro- 1H- 1,2,4-triazol- 1 -yl }methyl)- 1 -[3-(trifluoromethyl)pyridin-2-yl] - 1H- 1,2,4-triazole-5-carboxylate (150 mg, 253 pmol) in DMF (1.0 ml) was treated with <strong>[147688-58-2]2,2-<strong>[147688-58-2]dimethylmorpholine</strong></strong> (292mg, 2.53 mmol) and N,N-diisopropylethylamine (88 p1, 510 pmol). The resulting mixture wasstirred 8 h at 40C under microwave irradiation. The reaction mixture was diluted with ethyl acetate and washed with an aqueous hydrochloric acid solution (iN). The aqueous phase was extracted 3 times with ethyl acetate and the combined organic layers were evaporated. The residue was purified by preparative HPLC (Method 11) and evaporated. The residue was purified a secondtime by preparative HPLC (Method 11). Third purification by preparative HPLC (Method 11) afforded 26.6 mg (89 % purity, 14 % of th.) of the title compound.LC-MS (Method 1): R = 1.04 mm; MS (ESIpos): mlz = 675.6 [M+H]?H-NMR (400 MHz , DMSO-d6) oe [ppm]: 8.84 (d, 1H), 8.58-8.46 (m, 1H), 7.91-7.83 (m, 1H), 7.79-7.56 (m, 4H), 6.89 (dd, 1H), 5.30-5.10 (m, 2H), 4.25 - 4.22 (br m, 1H), 4.05-3.24 (m, 8H,overlap with HDO peak), 1.17-0.99 (m, 6H).
  • 61
  • 3-chloro-2-[3-({3-(4-chlorophenyl)-5-oxo-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-4,5-dihydro-1H-1,2,4-triazol-1-yl}methyl)-1H-1,2,4-triazol-1-yl]benzoic acid [ No CAS ]
  • [ 147688-58-2 ]
  • 2-[(1-{2-chloro-6-[(2,2-dimethylmorpholin-4-yl)carbonyl]phenyl}-1H-1,2,4-triazol-3-yl)methyl]-5-(4-chlorophenyl)-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-2,4-dihydro-3H-1,2,4-triazol-3-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
40% A solution of 3-chloro-2-[3-({3-(4-chlorophenyl)-5-oxo-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]- 4,5-dihydro-lH-l,2,4-triazol-l-yl}methyl)-lH-l,2,4-triazol-l-yl]benzoic acid (Example 51A,120 mg, 221 muiotaetaomicron) in N,N-dimethylformamide (1.2 ml) was treated with HATU (126 mg, 331 muiotaetaomicron) and stirred 3 h at room temperature. <strong>[147688-58-2]2,2-<strong>[147688-58-2]dimethylmorpholine</strong></strong> (38.2 mg, 331 muiotaetaomicron) was added followed by N,N-diisopropylethylamine (120 mu, 660 muiotaetaomicron). The resulting mixture was stirred overnight at room temperature. Purification by preparative HPLC (Method 4) afforded 57.1 mg (40 % of th.) of the title compound. LC-MS (Method 2): Rt = 1.86 min; MS (ESIpos): m/z = 640. [M+H]+ -NMR (400 MHz, DMSO-d6) delta [ppm]: 8.83 (s, 1H), 7.85-7.42 (m, 7H), 6.91 (dd, 1H), 5.08 (s, 2H), 4.39 - 4.22 (br m, 1H), 4.09-2.59 (m, 8H, overlap with HDO peak), 1.20-0.73 (m, 6H).
  • 62
  • 3-[3-({3-(4-chlorophenyl)-5-oxo-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-4,5-dihydro-1H-1,2,4-triazol-1-yl}methyl)-1H-1,2,4-triazol-1-yl]pyridine-2-carboxylic acid [ No CAS ]
  • [ 147688-58-2 ]
  • 5-(4-chlorophenyl)-2-[(1-{2-[(2,2-dimethylmorpholin-4-yl)carbonyl]pyridin-3-yl}-1H-1,2,4-triazol-3-yl)methyl]-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-2,4-dihydro-3H-1,2,4-triazol-3-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
63% A solution of 3-[3-({3-(4-chlorophenyl)-5-oxo-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-4,5- dihydro- 1 H- 1 ,2,4-triazol- 1 -yl } methyl)- 1H- 1 ,2,4-triazol- 1 -yl]pyridine-2-carboxylic acid (Example 11A, 100 mg, 196 muiotaetaomicron) in N,N-dimethylformamide (1.0 ml, 13 mmol) was treated with HATU (112 mg, 294 muiotaetaomicron) and stirred 1 h at room temperature. 2,2-Dimethylmorpholine (33.9 mg, 294 muiotaetaomicron) was then added followed by and N,N-diisopropylethylamine (100 mu, 590 muiotaetaomicron). The resulting mixture was stirred overnight at room temperature, diluted with water and purified by preparative HPLC (Method 4) affording 75.1 mg (63 % of th.) of the title compound. Mixture of rotamers LC-MS (Method 2): Rt = 1.61 min; MS (ESIpos): m/z = 607.1 [M+H]+ -NMR (400 MHz, DMSO-d6) delta [ppm]: 9.04-8.93 (m, 1H), 8.76-8.61 (m, 1H), 8.28-8.17 (m, 1H), 7.83-7.55 (m, 5H), 6.96-6.85 (m, 1H), 5.16-5.01 (m, 2H), 4.41 - 4.22 (br m, 1H), 4.04-3.78 (m, 2H), 3.63-3.48 (m, 2H), 3.47-3.18 (m, 2H, overlap with HDO peak), 3.13-2.82 (m, 2H), 1.20- 0.88 (m, 6H).
  • 63
  • 3-[3-({3-(4-chlorophenyl)-5-oxo-4-[(2R)-3,3,3-trifluoro-2-hydroxypropyl]-4,5-dihydro-1H-1,2,4-triazol-1-yl}methyl)-1H-1,2,4-triazol-1-yl]pyridine-2-carboxylic acid [ No CAS ]
  • [ 147688-58-2 ]
  • 5-(4-chlorophenyl)-2-[(1-{2-[(2,2-dimethylmorpholin-4-yl)carbonyl]pyridin-3-yl}-1H-1,2,4-triazol-3-yl)methyl]-4-[(2R)-3,3,3-trifluoro-2-hydroxypropyl]-2,4-dihydro-3H-1,2,4-triazol-3-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
29% A solution of 3-[3-({3-(4-chlorophenyl)-5-oxo-4-[(2R)-3,3,3-trifluoro-2-hydroxypropyl]-4,5- dihydro- 1 H- 1 ,2,4-triazol- 1 -yl } methyl)- 1H- 1 ,2,4-triazol- 1 -yl]pyridine-2-carboxylic acid (Example 12A, 100 mg, 196 muiotaetaomicron) in Nu,Nu-dimethylformamide (1 ml, 13 mmol) was treated with HATU (112 mg, 294 muiotaetaomicron) and stirred 1 h at room temperature. 2,2-Dimethylmorpholine (33.9 mg, 294 muiotaetaomicron) was then added followed by and N,N-diisopropylethylamine (100 mu, 590 muiotaetaomicron). The resulting mixture was stirred overnight at room temperature, diluted with water and purified by preparative HPLC (Method 4) affording 38.0 mg (29 % of th.) of the title compound. LC-MS (Method 2): Rt = 1.65 min; MS (ESIpos): m/z = 607.2 [M+H]+ -NMR (400 MHz, DMSO-d6) delta [ppm]: 9.06-8.90 (m, 1H), 8.80-8.64 (m, 1H), 8.29-8.15 (m, 1H), 7.81-7.51 (m, 5H), 6.99-6.78 (m, 1H), 5.16-4.99 (m, 2H), 4.42-4.21 (m, 1H), 4.10-3.78 (m, 2H), 3.73-3.48 (m, 2H), 3.45-3.22 (m, 2H, overlap with HDO peak), 3.13-2.79 (m, 2H), 1.22-0.88 (m, 6H).
  • 64
  • 6-(4,6-difluoro-2-pyridyl)-5-methyl-2-pyrimidin-2-yl-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine [ No CAS ]
  • [ 147688-58-2 ]
  • 4-[2-fluoro-6-(5-methyl-2-pyrimidin-2-yl-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-6-yl)-4-pyridyl]-2,2-dimethylmorpholine [ No CAS ]
  • 4-[4-fluoro-6-(5-methyl-2-pyrimidin-2-yl-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-6-yl)-2-pyridyl]-2,2-dimethylmorpholine [ No CAS ]
YieldReaction ConditionsOperation in experiment
21.5 mg; 11.2 mg With potassium carbonate; In N,N-dimethyl acetamide; at 110 - 130℃; for 30h; A mixture of 6-(4,6-difluoro-2-pyridyl)-5-methyl-2-pyrimidin-2-yl-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine (one product of step 7 in Example 1 , 80.0 mg, 0.235 mmol), 2,2- <strong>[147688-58-2]dimethylmorpholine</strong> (81.2 mg, 0.705 mmol) and K2CO3(97.4 mg, 0.705 mmol) in DMA (3 mL) was heated at 110 C for 15 hrs, and at 130 C for 15 hrs. The resulting mixture was poured into brine (4 mL), and extracted with DCM (3 mL) for 4 times. The combined organic layers were washed sequentially with water and brine, dried over anhydrous Na2S04and concentrated in vacuo. The residue was purified by prep-HPLC to afford 4-[2-fluoro-6-(5-methyl-2-pyrimidin-2-yl-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-6-yl)-4-pyridyl]-<strong>[147688-58-2]2,2-<strong>[147688-58-2]dimethyl-morpholine</strong></strong> (21.5 mg) as a light yellow solid and 4-[4-fluoro-6-(5-methyl-2-pyrimidin-2-yl-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-6-yl)-2-pyridyl]-<strong>[147688-58-2]2,2-<strong>[147688-58-2]dimethyl-morpholine</strong></strong> (11.2 mg) as a yellow solid.Example 8: 4-[2-fluoro-6-(5-methyl-2-pyrimidin-2-yl-7,8-dihydro-5H-pyrido[4,3- d]pyrimidin-6-yl)-4-pyridyl]-<strong>[147688-58-2]2,2-<strong>[147688-58-2]dimethyl-morpholine</strong></strong>, 1H NMR (400 MHz CDC13) delta ppm: 9.00 - 9.05 (m, 2 H), 8.81 (s, 1 H), 7.41 - 7.45 (m, 1 H), 5.76 - 5.80 (m, 1 H), 5.68 - 5.73 (m, 1 H), 5.67 (s, 1 H), 4.32 - 4.42 (m, 1 H), 3.81 - 3.90 (m, 2 H), 3.41 - 3.53 (m, 1 H), 3.19 - 3.33 (m, 4 H), 3.11 (s, 2 H), 1.53 - 1.59 (m, 3 H), 1.30 (s, 6 H). MS obsd. (ESI+) [(M+H)+]: 436.Example 9: 4-[4-fluoro-6-(5-methyl-2-pyrimidin-2-yl-7,8-dihydro-5H-pyrido[4,3- d]pyrimidin-6-yl)-2-pyridyl]-<strong>[147688-58-2]2,2-<strong>[147688-58-2]dimethyl-morpholine</strong></strong>, 1H NMR (400 MHz CDC13) delta ppm: 9.03 (d, 2 H), 8.81 (s, 1 H), 7.41 - 7.46 (m, 1 H), 5.77 - 5.83 (m, 1 H), 5.65 - 5.72 (m, 1 H), 5.56 - 5.64 (m, 1 H), 4.37 - 4.48 (m, 1 H), 3.79 - 3.90 (m, 2 H), 3.39 - 3.61 (m, 3 H), 3.17 - 3.36 (m, 4 H), 1.57 (d, 3 H), 1.30 (s, 6 H). MS obsd. (ESI+) [(M+H)+]: 436.
  • 65
  • lithium 5-amino-7-methoxyimidazo[1,2-c]quinazoline-2-carboxylate [ No CAS ]
  • [ 147688-58-2 ]
  • (5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)(2,2-dimethylmorpholino)methanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
In N,N-dimethyl-formamide; at 20℃; General procedure: Additional amide analogs were prepared by adding 1.5 equivalents of an amine which will provide the desired substituents into a 1 dram vial (1.5 eq.) along with lithium 5-amino-7- methoxyimidazo[1,2-c]quinazoline-2-carboxylate (30 mg, 0.114 mmol) and a DMF solution (1.0 ml) solution of DIPEA (0.079 ml, 0.454 mmol), shaking the vial for 5 minutes in a Bohdan Miniblock Shaker and then adding 1-propanephosphonic acid cyclic anhydride (50% w/w in EtOAc, 64.7 mul, 0.109 mmol), and continuing to shake the vial at RT overnight. The completed reaction was quenched with 1.0 ml water and the organic layer separated by filtering through a Varian 2 ml Reservior Frit and a Whatman 0.45mum syringe filter to remove emulsion, followed by solvent removal using a Genevac. The crude residue was dissolved in 1.0 ml DMSO and purified by LC/MS.
  • 66
  • 5-bromo-1-[(1S,2S)-2-methyl-1-(5-oxo-4H-1,2,4-oxadiazol-3-yl)cyclopropyl]indole-2-carboxylic acid [ No CAS ]
  • [ 147688-58-2 ]
  • 5-(2,2-dimethylmorpholin-4-yl)-1-[(1S,2S)-2-methyl-1-(5-oxo-4H-1,2,4-oxadiazol-3-yl)cyclopropyl]indole-2-carboxylic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
96% With bis(dibenzylideneacetone)-palladium(0); sodium t-butanolate; ruphos; In 1-methyl-pyrrolidin-2-one; at 100℃; for 0.5h;Inert atmosphere; Step 7-1. 5-(2,2-Dimethylmorpholin-4-yl)-1-[(1S,2S)-2-methyl-1-(5-oxo-4H-1,2,4-oxadiazol-3-yl)cyclopropyl]indole-2-carboxylic acid (Compound 7b) The NMP (44 mL) suspension of <strong>[147688-58-2]2,2-<strong>[147688-58-2]dimethylmorpholine</strong></strong> (Compound 7a, 1.98 g, 17.2 mmol), tris (dibenzylideneacetone)dipalladium(0) (0.121 g, 0.132 mmol), 2-dicyclohexylphosphino-2',6'-di-i-propoxy-1,1'-biphenyl (0.123 g, 0.264 mmol), sodium tert-butoxide (5.08 g, 529 mmol) was deaerated at room temperature under reduced pressure, then, nitrogen was introduced in the vessel. Under nitrogen atmosphere, Compound 6f (5.0 g, 13.2 mmol) obtained in Step 6-4 was added to the suspension, and the mixture was stirred at 100 C. for 0.5 h. then cooled to room temperature. Formic acid was added to the mixture, and the resulting product was directly purified by reversed-phase chromatography (acetonitrile/water, 0.1% formic acid) to obtain the titled Compound 7b (5.26 g, yield 96%).
  • 67
  • [ 147688-58-2 ]
  • [ 149524-45-8 ]
  • (S)-N-((3-(4-(2,2-dimethylmorpholino)-3-fluorophenyl)-2-oxooxazolidin-5-yl)methyl)acetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
28% With potassium phosphate; copper(I) bromide; 1,1'-bi-2-naphthol; In N,N-dimethyl-formamide; at 80℃;Glovebox; Sealed tube; Inert atmosphere; General procedure: To a flame-dried one-dram vial equipped with a Teflon screw cap and a stir bar was addedCuBr (0.1 - 0.3 equiv), BINOL (0.1 - 0.3 equiv), aryl iodide 7 (1 equiv), and K3PO4 (2equiv). The vial was cycled into a glovebox and then DMF (0.2 M final concentration) wasadded to the vial, followed by the amine (2 equiv). The reaction was stirred at 80 C for24-72 hours until complete consumption of starting material was noted by LC-MS analysis.In some cases, conversion of the starting material stopped, at which point 0.2 equiv of CuBrand 0.2 equiv of BINOL was added to the reaction, which then proceeded to completion.The reaction was diluted with EtOAc and filtered through a plug of silica, rinsing with 10%MeOH/EtOAc. The solution was concentrated in vacuo until all DMF solvent wasremoved. The crude material was purified by by silica gel flash chromatography or reversephase prep HPLC to afford the desired linezolid analog.
  • 68
  • [ 147688-58-2 ]
  • methyl (S)-3-(5-bromopyridin-3-yl)-3-((tert-butoxycarbonyl)amino)propanoate [ No CAS ]
  • (S)-methyl 3-(tert-butoxycarbonylamino)-3-(5-(2,2-dimethylmorpholino)pyridin-3-yl)propanoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With palladium diacetate; caesium carbonate; XPhos; In toluene; at 120℃; for 16h;Inert atmosphere; A mixture of (S)-methyl 3-(5-bromopyridin-3-yl)-3-(tert-butoxycarbonylamino)propanoate (150 mg, 0.42 mmol), <strong>[147688-58-2]2,2-<strong>[147688-58-2]dimethylmorpholine</strong></strong> (96 mg, 0.84 mmol), Pd(OAc)2 (9 mg, 0.04 mmol), X-Phos (40 mg, 0.08 mmol) and Cs2CO3 (408 mg, 1.25 mmol) in toluene (2 mL) was stirred at 120 C. for 16 hours under N2 atmosphere. The mixture was cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure to give a residue, which was purified by Preparative-TLC (EtOAc:Petroleum ether=1:2) to obtain the desired product (S)-methyl 3-(tert-butoxycarbonylamino)-3-(5-(2,2-dimethylmorpholino)pyridin-3-yl)propanoate as a colorless oil (88 mg). Yield 54% (21% purity, UV=214 nm, ESI 394 (M+H)+).
  • 69
  • [ 147688-58-2 ]
  • 2,2-dimethyl-4-(4-(2-methyl-5-(pyridin-4-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)morpholine [ No CAS ]
YieldReaction ConditionsOperation in experiment
Compound 120 was synthesized in a similar manner as depicted in Scheme 35, Step 3, using <strong>[147688-58-2]2,2-<strong>[147688-58-2]dimethylmorpholine</strong></strong>.
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