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

HRID 2392259Notes

Reaction equation

HRID 2392259 reaction equation
[CH2:1]([N:3]1[C:7]([C:8]2[CH:9]=[C:10]([C:13]([OH:15])=O)[S:11][CH:12]=2)=[C:6]([CH3:16])[CH:5]=[N:4]1)[CH3:2].F[P-](F)(F)(F)(F)F.Br[P+](N1CCCC1)(N1CCCC1)N1CCCC1.CCN(C(C)C)C(C)C.[NH2:50][C@@H:51]([CH2:64]/[C:65](/[C:69](/[C:72]([F:75])([F:74])[F:73])=[CH:70]\[CH3:71])=[CH:66]/[CH:67]=C)[CH2:52][N:53]1[C:61](=[O:62])[C:60]2[C:55](=[CH:56][CH:57]=[CH:58][CH:59]=2)[C:54]1=[O:63]>>[O:63]=[C:54]1[C:55]2[C:60](=[CH:59][CH:58]=[CH:57][CH:56]=2)[C:61](=[O:62])[N:53]1[CH2:52][C@@H:51]([NH:50][C:13]([C:10]1[S:11][CH:12]=[C:8]([C:7]2[N:3]([CH2:1][CH3:2])[N:4]=[CH:5][C:6]=2[CH3:16])[CH:9]=1)=[O:15])[CH2:64][C:65]1[CH:66]=[CH:67][CH:71]=[CH:70][C:69]=1[C:72]([F:74])([F:75])[F:73]

Participants

5

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 578267904-(1-ethyl-4-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxylic AcidHCID 866335682-{(2S,4Z)-2-amino-4-[(1E)-1-(trifluoromethyl)-1-propen-1-yl]-4,6-heptadien-1-yl}-1H-isoindole-1,3(2H)-dione

Product 1

HCID 57826403N-((1S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-{[2-(trifluoromethyl)phenyl]methyl}ethyl)-4-(1-ethyl-4-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxamideYield 63.2%

Procedure

To a mixture of 4-(1-ethyl-4-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxylic acid (240 mg, 1.02 mmol) and bromo-tris-pyrrolidino phosphoniumhexafluorophosphate (Pybrop) (568 mg, 1.22 mmol) was added DIPEA (1.77 ml, 10.16 mmol). After 10 min, 2-{(2S,4Z)-2-amino-4-[(1E)-1-(trifluoromethyl)-1-propen-1-yl]-4,6-heptadiene-1-yl}-1H-isoindole-1,3(2H)-dione (425 mg, 1.22 mmol) was added. After 2 h, the solution was concentrated and purified via column chromatography (silica, 20-50% EtOAc/Hexane) affording the title compound (365 mg, 63%) as a white solid: LC-MS (ES) m/z 567 (M+H)+.

Workup

  1. waitAfter 2 h
  2. concentrationthe solution was concentrated
  3. custompurified via column chromatography (silica, 20-50% EtOAc/Hexane)

Sources & evidence

ORD record
ord-4d1b0e9e10c24a079b2eab61e890aeaf
Source dataset
uspto-grants-2012_09
Patent number
US08273782B2

Reaction notes

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