N-methyl-2-pyrrolidone → 8-(2,4-dimethoxybenzyl)-4-(4-(1-(2-(pyrrolidin-1-yl)ethyl)-4-(trifluoromethyl)-1H-imidazol-2-yl)piperidin-1-yl)-5-(trifluoromethyl)-5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-one

HRID 2088902Notes

Reaction equation

HRID 2088902 reaction equation
Cl[C:2]1[C:3]2[CH:11]([C:12]([F:15])([F:14])[F:13])[CH2:10][C:9](=[O:16])[N:8]([CH2:17][C:18]3[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][C:19]=3[O:26][CH3:27])[C:4]=2[N:5]=[CH:6][N:7]=1.Cl.Cl.Cl.[N:31]1([CH2:36][CH2:37][N:38]2[CH:42]=[C:41]([C:43]([F:46])([F:45])[F:44])[N:40]=[C:39]2[CH:47]2[CH2:52][CH2:51][NH:50][CH2:49][CH2:48]2)[CH2:35][CH2:34][CH2:33][CH2:32]1.CN1CCCC1=O.C(N(C(C)C)CC)(C)C>O>[CH3:27][O:26][C:19]1[CH:20]=[C:21]([O:24][CH3:25])[CH:22]=[CH:23][C:18]=1[CH2:17][N:8]1[C:4]2[N:5]=[CH:6][N:7]=[C:2]([N:50]3[CH2:49][CH2:48][CH:47]([C:39]4[N:38]([CH2:37][CH2:36][N:31]5[CH2:32][CH2:33][CH2:34][CH2:35]5)[CH:42]=[C:41]([C:43]([F:45])([F:46])[F:44])[N:40]=4)[CH2:52][CH2:51]3)[C:3]=2[CH:11]([C:12]([F:13])([F:14])[F:15])[CH2:10][C:9]1=[O:16]

Participants

6

Reactant 4

HCID 13387N-methyl-2-pyrrolidoneHCID 81531DiisopropylethylamineHCID 866665684-Chloro-8-(2,4-dimethoxybenzyl)-5-(trifluoromethyl)-5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-oneHCID 866665764-(1-(2-(pyrrolidin-1-yl)ethyl)-4-(trifluoromethyl)-1H-imidazol-2-yl)piperidine trihydrochloride

Product 1

HCID 885311538-(2,4-dimethoxybenzyl)-4-(4-(1-(2-(pyrrolidin-1-yl)ethyl)-4-(trifluoromethyl)-1H-imidazol-2-yl)piperidin-1-yl)-5-(trifluoromethyl)-5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-one

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
220 °C

Procedure

Combine 4-chloro-8-(2,4-dimethoxybenzyl)-5-(trifluoromethyl)-5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-one (0.65 g, 1.62 mmol), 4-(1-(2-(pyrrolidin-1-yl)ethyl)-4-(trifluoromethyl)-1H-imidazol-2-yl)piperidine trihydrochloride (0.76 g, 1.1 eq), N-methylpyrrolidinone (20 mL) and diisopropylethylamine (1.69 mL, 6.0 eq) in a sealed vessel. Heat at 220° C. for 30 minutes. Dilute the reaction mixture with water and extract with ethyl acetate. Wash the organics with saturated aqueous sodium chloride. Dry the organics over anhydrous sodium sulfate, filter, and concentrate in vacuo. Purify by normal phase chromatography, eluting with a 1-10% methanol/dichloromethane gradient, to give crude 8-(2,4-dimethoxybenzyl)-4-(4-(1-(2-(pyrrolidin-1-yl)ethyl)-4-(trifluoromethyl)-1H-imidazol-2-yl)piperidin-1-yl)-5-(trifluoromethyl)-5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-one (crude).

Workup

  1. extractionextract with ethyl acetate
  2. washWash the organics with saturated aqueous sodium chloride
  3. dry with materialDry the organics over anhydrous sodium sulfate
  4. filtrationfilter
  5. concentrationconcentrate in vacuo
  6. customPurify by normal phase chromatography
  7. washeluting with a 1-10% methanol/dichloromethane gradient

Sources & evidence

ORD record
ord-412f2d4b4ebd405d84e1a3cab01b5dc4
Source dataset
uspto-grants-2013_05
Patent number
US08436002B2

Reaction notes

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