Water → HCID 59614338, compound

HRID 409442Notes

Reaction equation

HRID 409442 reaction equation
[F:1][C:2]([F:35])([F:34])[C:3]1[CH:4]=[C:5]([CH:27]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:29]=1)[CH2:6][N:7]([C@H:20]1[CH2:24][C@@H:23]([CH2:25][CH3:26])[NH:22][CH2:21]1)[C:8]1[N:13]=[CH:12][C:11]([C:14]2[CH:15]=[N:16][N:17]([CH3:19])[CH:18]=2)=[CH:10][N:9]=1.F[C:37]1[CH:44]=[CH:43][C:42]([C:45]([F:48])([F:47])[F:46])=[CH:41][C:38]=1[CH:39]=[O:40].C([O-])([O-])=O.[K+].[K+].O>CN(C=O)C.CCOC(C)=O>[F:35][C:2]([F:34])([F:1])[C:3]1[CH:4]=[C:5]([CH:27]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:29]=1)[CH2:6][N:7]([C:8]1[N:9]=[CH:10][C:11]([C:14]2[CH:15]=[N:16][N:17]([CH3:19])[CH:18]=2)=[CH:12][N:13]=1)[C@@H:20]1[CH2:21][N:22]([C:37]2[CH:44]=[CH:43][C:42]([C:45]([F:46])([F:48])[F:47])=[CH:41][C:38]=2[CH:39]=[O:40])[C@H:23]([CH2:25][CH3:26])[CH2:24]1

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 27349042-Fluoro-5-(trifluoromethyl)benzaldehydeHCID 59614335HCID 59614335, compound

Product 1

HCID 59614338HCID 59614338, compoundYield 76.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of [3,5-bis(trifluoromethyl)benzyl]-((3S,5R)-5-ethyl-pyrrolidin-3-yl)-[5-(1-methyl-1H-pyrazol-4-yl)-pyrimidin-2-yl]-amine (75 mg, 0.15 mmol), 2-fluoro-5-trifluoromethyl-benzaldehyde (44 mg, 0.23 mmol) and K2CO3 (42 mg, 0.30 mmol) in DMF (1.5 mL) is heated at 130° C. and stirred for 2 hours. After the mixture is cooled down until room temperature, H2O and EtOAc is added and then extracted with EtOAc. The combined organic layer is dried over MgSO4, then concentrated under reduced pressure. The obtained residue is purified by silica gel column chromatography (eluent: n-hexane/EtOAc) to give 2-((2R,4S)-4-{[3,5-bis(trifluoromethyl)benzyl]-[5-(1-methyl-1H-pyrazol-4-yl)-pyrimidin-2-yl]-amino}-2-ethyl-pyrrolidin-1-yl)-5-trifluoromethyl-benzaldehyde as a colorless oil (77 mg, 74%). ESI-MS m/z: 670 [M+1]+, Retention time 2.75 min (condition A).

Workup

  1. temperatureAfter the mixture is cooled down until room temperature
  2. extractionextracted with EtOAc
  3. dry with materialThe combined organic layer is dried over MgSO4
  4. concentrationconcentrated under reduced pressure
  5. customThe obtained residue is purified by silica gel column chromatography (eluent: n-hexane/EtOAc)

Sources & evidence

ORD record
ord-35e0ceac11294f6b9db76470c156fd6e
Source dataset
uspto-grants-2014_06
Patent number
US08759365B2

Reaction notes

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