Diisopropylethylamine → 2-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-N-(2-oxo-2-(2,2,2-trifluoroethylamino)ethyl)thieno[2,3-b]pyridine-5-carboxamide

HRID 240891Notes

Reaction equation

HRID 240891 reaction equation
[NH2:1][CH2:2][C:3]([NH:5][CH2:6][C:7]([F:10])([F:9])[F:8])=[O:4].[Cl:11][C:12]1[CH:13]=[C:14]([C:19]2([C:36]([F:39])([F:38])[F:37])[O:23][N:22]=[C:21]([C:24]3[S:35][C:27]4=[N:28][CH:29]=[C:30]([C:32](O)=[O:33])[CH:31]=[C:26]4[CH:25]=3)[CH2:20]2)[CH:15]=[C:16]([Cl:18])[CH:17]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>>[Cl:18][C:16]1[CH:15]=[C:14]([C:19]2([C:36]([F:38])([F:37])[F:39])[O:23][N:22]=[C:21]([C:24]3[S:35][C:27]4=[N:28][CH:29]=[C:30]([C:32]([NH:1][CH2:2][C:3](=[O:4])[NH:5][CH2:6][C:7]([F:10])([F:9])[F:8])=[O:33])[CH:31]=[C:26]4[CH:25]=3)[CH2:20]2)[CH:13]=[C:12]([Cl:11])[CH:17]=1

Participants

5

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 247051432-Amino-N-(2,2,2-trifluoroethyl)acetamideHCID 714691762-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]thieno[2,3-b]pyridine-5-carboxylic acid

Product 1

HCID 714691772-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-N-(2-oxo-2-(2,2,2-trifluoroethylamino)ethyl)thieno[2,3-b]pyridine-5-carboxamideYield 34.8%

Procedure

Stir a mixture of 2-Amino-N-(2,2,2-trifluoro-ethyl)-acetamide (156 mg, 1 mmol), 2-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-thieno[2,3-b]pyridine-5-carboxylic acid (160 mg, 0.24 mmol), HATU (150 mg, 0.39 mmol) and DIPEA (0.2 mL) at room temperature for 10 hours. After removal of solvent, purify the mixture by preparative-HPLC to afford 2-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-N-(2-oxo-2-(2,2,2-trifluoroethylamino)ethyl)thieno[2,3-b]pyridine-5-carboxamide as a white solid (50 mg, 34.78%). MS (m/z): 599 (M+1). 1H NMR (400 MHz, CDCl3) δ 9.02 (s, 1H), 8.51 (s, 1H), 7.52 (s, 2H), 7.44-7.41 (m, 2H), 7.22 (s, 1H), 6.64 (s, 1H), 4.27 (d, J=5.2, 2H), 4.17 (d, J=16.8, 1H), 4.04-3.95 (m, 2H), 3.80 (d, J=16.08, 1H).

Workup

  1. customAfter removal of solvent
  2. custompurify the mixture by preparative-HPLC

Sources & evidence

ORD record
ord-9045523e81f14e438f611f0ca6ece7f6
Source dataset
uspto-grants-2014_02
Patent number
US08648081B2

Reaction notes

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