Diisopropylethylamine → N-((1S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-{[2-(trifluoromethyl)phenyl]methyl}ethyl)-4-(1-methyl-1H-pyrazol-5-yl)-5-(trifluoromethyl)-2-thiophenecarboxamide

HRID 1845658Notes

Reaction equation

HRID 1845658 reaction equation
[CH3:1][N:2]1[C:6]([C:7]2[CH:8]=[C:9]([C:16]([OH:18])=O)[S:10][C:11]=2[C:12]([F:15])([F:14])[F:13])=[CH:5][CH:4]=[N:3]1.F[P-](F)(F)(F)(F)F.[PH4+].CCN(C(C)C)C(C)C.[NH2:36][C@@H:37]([CH2:50][C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][C:52]=1[C:57]([F:60])([F:59])[F:58])[CH2:38][N:39]1[C:47](=[O:48])[C:46]2[C:41](=[CH:42][CH:43]=[CH:44][CH:45]=2)[C:40]1=[O:49]>C(Cl)Cl>[O:48]=[C:47]1[C:46]2[C:41](=[CH:42][CH:43]=[CH:44][CH:45]=2)[C:40](=[O:49])[N:39]1[CH2:38][C@@H:37]([NH:36][C:16]([C:9]1[S:10][C:11]([C:12]([F:13])([F:14])[F:15])=[C:7]([C:6]2[N:2]([CH3:1])[N:3]=[CH:4][CH:5]=2)[CH:8]=1)=[O:18])[CH2:50][C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][C:52]=1[C:57]([F:59])([F:58])[F:60]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 21584439Phosphonium hexafluorophosphateHCID 578267784-(1-methyl-1H-pyrazol-5-yl)-5-(trifluoromethyl)-2-thiophenecarboxylic AcidHCID 578268082-{(2S)-2-amino-3-[2-(trifluoromethyl)phenyl]propyl}-1H-isoindole-1,3(2H)-dione

Product 1

HCID 57826525N-((1S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-{[2-(trifluoromethyl)phenyl]methyl}ethyl)-4-(1-methyl-1H-pyrazol-5-yl)-5-(trifluoromethyl)-2-thiophenecarboxamideYield 93.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

At room temperature, a mixture of 4-(1-methyl-1H-pyrazol-5-yl)-5-(trifluoromethyl)-2-thiophenecarboxylic acid (235 mg, 80% purity, 0.68 mmol), phosphoniumhexafluorophosphate (PyBrOP) (381 mg, 0.19 mmol), DIPEA (0.59 mL, 3.4 mmol) and 2-{(2S)-2-amino-3-[2-(trifluoromethyl)phenyl]propyl}-1H-isoindole-1,3(2H)-dione (261 mg, 0.75 mmol) in DCM (5 mL) was stirred for 2 h. The reaction solution was concentrated and purified via column chromatography (silica, 20-50% EtOAc/Hexane) affording the title compound (386 mg, 86%) as a white solid: LC-MS (ES) 607 (M+H)+.

Workup

  1. concentrationThe reaction solution was concentrated
  2. custompurified via column chromatography (silica, 20-50% EtOAc/Hexane)

Sources & evidence

ORD record
ord-c65aeaca1ecf4d40af51d8a71120f744
Source dataset
uspto-grants-2015_02
Patent number
US08946278B2

Reaction notes

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