Diisopropylethylamine → tert-butyl (4-(4-((3-((4S)-4-(dimethylamino)-2-oxopyrrolidin-1-yl)-1-methyl-1H-pyrazol-4-yl)carbamoyl)-1,3-oxazol-2-yl)pyridin-2-yl)(2,2,2-trifluoroethyl)carbamate

HRID 632783Notes

Reaction equation

HRID 632783 reaction equation
[NH2:1][C:2]1[C:3]([N:8]2[CH2:12][C@@H:11]([N:13]([CH3:15])[CH3:14])[CH2:10][C:9]2=[O:16])=[N:4][N:5]([CH3:7])[CH:6]=1.[C:17]([O:21][C:22]([N:24]([CH2:39][C:40]([F:43])([F:42])[F:41])[C:25]1[CH:30]=[C:29]([C:31]2[O:32][CH:33]=[C:34]([C:36](O)=[O:37])[N:35]=2)[CH:28]=[CH:27][N:26]=1)=[O:23])([CH3:20])([CH3:19])[CH3:18].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>CN(C=O)C.O>[CH3:15][N:13]([CH3:14])[C@@H:11]1[CH2:12][N:8]([C:3]2[C:2]([NH:1][C:36]([C:34]3[N:35]=[C:31]([C:29]4[CH:28]=[CH:27][N:26]=[C:25]([N:24]([CH2:39][C:40]([F:42])([F:41])[F:43])[C:22](=[O:23])[O:21][C:17]([CH3:20])([CH3:19])[CH3:18])[CH:30]=4)[O:32][CH:33]=3)=[O:37])=[CH:6][N:5]([CH3:7])[N:4]=2)[C:9](=[O:16])[CH2:10]1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 1180609712-(2-((Tert-butoxycarbonyl)(2,2,2-trifluoroethyl)amino)pyridin-4-yl)oxazole-4-carboxylic acidHCID 118061163(4S)-1-(4-amino-1-methyl-1H-pyrazol-3-yl)-4-(dimethylamino)pyrrolidin-2-one

Product 1

HCID 131735456tert-butyl (4-(4-((3-((4S)-4-(dimethylamino)-2-oxopyrrolidin-1-yl)-1-methyl-1H-pyrazol-4-yl)carbamoyl)-1,3-oxazol-2-yl)pyridin-2-yl)(2,2,2-trifluoroethyl)carbamateYield 34.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of (4S)-1-(4-amino-1-methyl-1H-pyrazol-3-yl)-4-(dimethylamino)pyrrolidin-2-one (69.9 mg), 2-(2-((tert-butoxycarbonyl)(2,2,2-trifluoroethyl)amino)pyridin-4-yl)-1,3-oxazole-4-carboxylic acid (146 mg) and HATU (143 mg) in DMF (1.57 mL) was added diisopropylethylamine (0.082 mL), and the mixture was stirred at room temperature for 1.5 hr. The reaction mixture was poured into water, and the mixture was extracted with ethyl acetate. The extract was washed successively with water, saturated aqueous sodium hydrogen carbonate solution and saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (NH, ethyl acetate/hexane) to give the title compound (63.7 mg).

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe extract was washed successively with water, saturated aqueous sodium hydrogen carbonate solution and saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (NH, ethyl acetate/hexane)

Sources & evidence

ORD record
ord-cbf4ae72a1334e5c8f45f56d2ca38f22
Source dataset
uspto-grants-2016_04
Patent number
US09321757B2

Reaction notes

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