Dimethylformamide → HCID 117899577, compound

HRID 522305Notes

Reaction equation

HRID 522305 reaction equation
[CH3:1][C:2]1([O:5][CH2:4]1)[CH3:3].C(N(CC)C(C)C)(C)C.Cl.[CH3:16][N:17]1[C:21]2[N:22]=[C:23]([C:52]#[N:53])[N:24]=[C:25]([C:26]3[CH:27]=[N:28][C:29]([O:36][CH2:37][CH:38]4[CH2:43][CH2:42][N:41]([C:44]([CH:46]5[CH2:51][CH2:50][NH:49][CH2:48][CH2:47]5)=[O:45])[CH2:40][CH2:39]4)=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:31]=3)[C:20]=2[CH:19]=[CH:18]1.CN(C=O)C>CCO.O>[OH:5][C:2]([CH3:4])([CH3:3])[CH2:1][N:49]1[CH2:48][CH2:47][CH:46]([C:44]([N:41]2[CH2:42][CH2:43][CH:38]([CH2:37][O:36][C:29]3[N:28]=[CH:27][C:26]([C:25]4[C:20]5[CH:19]=[CH:18][N:17]([CH3:16])[C:21]=5[N:22]=[C:23]([C:52]#[N:53])[N:24]=4)=[CH:31][C:30]=3[C:32]([F:34])([F:33])[F:35])[CH2:39][CH2:40]2)=[O:45])[CH2:51][CH2:50]1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 11208Isobutylene oxideHCID 81531DiisopropylethylamineHCID 117899560HCID 117899560, compound

Product 1

HCID 117899577HCID 117899577, compound

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
60 °C

Procedure

Isobutylene oxide (38 μL) and N,N-diisopropylethylamine (73 μL) were added to a solution of 7-methyl-4-[6-{[1-(piperidin-4-yl carbonyl)piperidin-4-yl]methoxy}-5-(trifluoromethyl)pyridin-3-yl]-7H-pyrrolo[2,3-d]pyrimidine-2-carbonitrile monohydrochloride (120 mg) in EtOH (2.4 mL)-DMF (0.5 mL) at room temperature, and the mixture was stirred at 60° C. overnight. The reaction mixture was cooled to room temperature, and EtAOc and water were added thereto. Extraction was performed on the mixture using EtOAc, and the extract was washed with saturated brine. The organic layer was dried over MgSO4 and filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by basic silica gel column chromatography (Hex:CHCl3=70:30 to 20:80), whereby 4-{6-[(1-{[1-(2-hydroxy-2-methylpropyl)piperidin-4-yl]carbonyl}piperidin-4-yl)methoxy]-5-(trifluoromethyl)pyridin-3-yl}-7-methyl-7H-pyrrolo[2,3-d]pyrimidine-2-carbonitrile (93 mg) was obtained as a solid.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionExtraction
  3. washthe extract was washed with saturated brine
  4. dry with materialThe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. customThe residue was purified by basic silica gel column chromatography (Hex:CHCl3=70:30 to 20:80)

Sources & evidence

ORD record
ord-27f43812e58b4685b9173e47cd584ea9
Source dataset
uspto-grants-2016_05
Patent number
US09328118B2

Reaction notes

Loading…