4-Chloro-6-(trifluoromethyl)pyrimidine → (S)-tert-butyl 2-(2-fluoro-4-(1-(6-(trifluoromethyl)pyrimidin-4-yl)-1H-pyrazole-4-carboxamido)phenyl)morpholine-4-carboxylate

HRID 571886Notes

Reaction equation

HRID 571886 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([NH:8][C:9]([C:11]2[CH:12]=[N:13][NH:14][CH:15]=2)=[O:10])[CH:5]=[CH:4][C:3]=1[C@@H:16]1[O:21][CH2:20][CH2:19][N:18]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:17]1.Cl[C:30]1[CH:35]=[C:34]([C:36]([F:39])([F:38])[F:37])[N:33]=[CH:32][N:31]=1>CS(C)=O>[F:1][C:2]1[CH:7]=[C:6]([NH:8][C:9]([C:11]2[CH:12]=[N:13][N:14]([C:30]3[CH:35]=[C:34]([C:36]([F:39])([F:38])[F:37])[N:33]=[CH:32][N:31]=3)[CH:15]=2)=[O:10])[CH:5]=[CH:4][C:3]=1[C@@H:16]1[O:21][CH2:20][CH2:19][N:18]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:17]1

Participants

4

Reactant 2

HCID 115428814-Chloro-6-(trifluoromethyl)pyrimidineHCID 71087137(S)-tert-butyl 2-(2-fluoro-4-(1H-pyrazole-4-carboxamido)phenyl)morpholine-4-carboxylate

Product 1

HCID 71087182(S)-tert-butyl 2-(2-fluoro-4-(1-(6-(trifluoromethyl)pyrimidin-4-yl)-1H-pyrazole-4-carboxamido)phenyl)morpholine-4-carboxylate

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
120 °C

Procedure

Under N2, (S)-tert-butyl 2-(2-fluoro-4-(1H-pyrazole-4-carboxamido)phenyl)morpholine-4-carboxylate (60 mg, 154 μmol, Eq: 1.00), 4-chloro-6-(trifluoromethyl)-pyrimidine (CAS 37552-81-1) (28 mg, 154 μmol, Eq: 1.00) and were combined in DMSO (2 ml). The orange solution was stirred at 120° C. over 1 hour. Control with TLC: the reaction was finished. At RT, the RM was partitioned between water and EtOAc; extracted; the organic layer was washed with water and brine; dried over MgSO4; filtered; concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 10 g, 15% to 60% EtOAc in heptane). Yellow solid (41 mg). MS: 535.7 ([M−H]−)

Workup

  1. customAt RT, the RM was partitioned between water and EtOAc
  2. extractionextracted
  3. washthe organic layer was washed with water and brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude material was purified by flash chromatography (silica gel, 10 g, 15% to 60% EtOAc in heptane)

Sources & evidence

ORD record
ord-f134b766870b431ebb437ef8aba72f6b
Source dataset
uspto-grants-2015_05
Patent number
US09029370B2

Reaction notes

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