Dimethylformamide → HCID 52913955, compound

HRID 2088930Notes

Reaction equation

HRID 2088930 reaction equation
CS(O[CH2:6][CH2:7][N:8]1[CH:12]=[C:11]([CH2:13][C:14]([F:17])([F:16])[F:15])[N:10]=[C:9]1[CH:18]1[CH2:23][CH2:22][N:21]([C:24]2[C:25]3[C@H:33]([C:34]([F:37])([F:36])[F:35])[CH2:32][C:31](=[O:38])[NH:30][C:26]=3[N:27]=[CH:28][N:29]=2)[CH2:20][CH2:19]1)(=O)=O.CN(C)C=O.[NH:44]1[CH2:47][CH2:46][CH2:45]1>C(OCC)(=O)C>[N:44]1([CH2:6][CH2:7][N:8]2[CH:12]=[C:11]([CH2:13][C:14]([F:17])([F:16])[F:15])[N:10]=[C:9]2[CH:18]2[CH2:19][CH2:20][N:21]([C:24]3[C:25]4[C@H:33]([C:34]([F:36])([F:35])[F:37])[CH2:32][C:31](=[O:38])[NH:30][C:26]=4[N:27]=[CH:28][N:29]=3)[CH2:22][CH2:23]2)[CH2:47][CH2:46][CH2:45]1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 10422AzetidineHCID 86666582HCID 86666582, compound

Product 1

HCID 52913955HCID 52913955, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

Combine (R)-2-(2-(1-(7-oxo-5-trifluoromethyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-4-yl)piperidin-4-yl)-4-(2,2,2-trifluoroethyl)-1H-imidazol-1-yl)ethyl methanesulfonate (1.04 g, 1.82 mmol), dimethylformamide (9.3 mL), and azetidine (1.11 mL, 9.0 eq) under nitrogen. Heat the reaction mixture at 50° C. overnight, then allow to cool to room temperature. Dilute with ethyl acetate. Wash the organic layer with water. Dry the organics over anhydrous sodium sulfate, filter, and concentrate in vacuo. Purify by normal phase chromatography, eluting with 10% methanol/dichloromethane to 10% 2 M ammonia in methanol/dichloromethane, to give the title compound, (R)-4-(4-(1-(2-(azetidin-1-yl)ethyl)-4-(2,2,2-trifluoroethyl)-1H-imidazol-2-yl)piperidin-1-yl)-5-(trifluoromethyl)-5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-one, as a white solid (0.49 g, 51%). MS (ES) m/z=532 [M]+.

Workup

  1. temperatureto cool to room temperature
  2. washWash the organic layer with water
  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 10% methanol/dichloromethane to 10% 2 M ammonia in methanol/dichloromethane

Sources & evidence

ORD record
ord-4e5ec0f3fc764868a963007d391251da
Source dataset
uspto-grants-2013_05
Patent number
US08436002B2

Reaction notes

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