Imidazole → HCID 70980765, compound

HRID 1409324Notes

Reaction equation

HRID 1409324 reaction equation
Br[CH2:2][C:3]1[O:7][N:6]=[C:5]([C:8]([NH:10][C@@H:11]([CH3:28])[CH2:12][N:13]2[CH:17]=[CH:16][C:15]([C:18]3[CH:23]=[C:22]([F:24])[C:21]([C:25]#[N:26])=[C:20]([Cl:27])[CH:19]=3)=[N:14]2)=[O:9])[CH:4]=1.[NH:29]1[CH:33]=[CH:32][N:31]=[CH:30]1>CN(C=O)C.CCOC(C)=O>[N:29]1([CH2:2][C:3]2[O:7][N:6]=[C:5]([C:8]([NH:10][C@@H:11]([CH3:28])[CH2:12][N:13]3[CH:17]=[CH:16][C:15]([C:18]4[CH:23]=[C:22]([F:24])[C:21]([C:25]#[N:26])=[C:20]([Cl:27])[CH:19]=4)=[N:14]3)=[O:9])[CH:4]=2)[CH:33]=[CH:32][N:31]=[CH:30]1

Participants

5

Reactant 2

HCID 795ImidazoleHCID 86714626HCID 86714626, compound

Product 1

HCID 70980765HCID 70980765, compoundYield 27.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

(S)-5-(Bromomethyl)-N-(1-(3-(3-chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)isoxazole-3-carboxamide (0.137 mmol, 0.064 g) was suspended in DMF (5 ml). Imidazole (2.74 mmol, 0.187 g) was added and the resulting mixture was stirred at RT for 2.5 h. The reaction mixture was heated to 60° C. for 1.5 h. The mixture was diluted with EtOAc and washed four times with water. The organic phase was dried, filtered and evaporated. The crude product was purified by preparative HPLC. 0.017 g of the title compound was obtained. 1H-NMR (400 MHz, DMSO-d6): δ 1.15 (d, 3H), 4.31 (d, 2H), 4.37-4.50 (m, 1H), 5.50 (s, 2H), 6.63 (s, 1H), 6.94 (s, 1H), 6.99 (d, 1H), 7.22-7.24 (m, 1H), 7.76 (s, 1H), 7.83 (d, 1H), 7.84-7.88 (m, 1H), 7.96 (s, 1H), 8.81 (d, 1H).

Workup

  1. temperatureThe reaction mixture was heated to 60° C. for 1.5 h
  2. washwashed four times with water
  3. customThe organic phase was dried
  4. filtrationfiltered
  5. customevaporated
  6. customThe crude product was purified by preparative HPLC

Sources & evidence

ORD record
ord-c42b63c0a1f74ef09fc9096a0e95270f
Source dataset
uspto-grants-2014_12
Patent number
US08921378B2

Reaction notes

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