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

HRID 1967118Notes

Reaction equation

HRID 1967118 reaction equation
[NH2:1][C@@H:2]([CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[C:22]([F:25])([F:24])[F:23])[CH2:3][N:4]1[C:12](=[O:13])[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]1=[O:14].[CH3:26][N:27]1[C:31]([C:32]2[N:36]([CH3:37])[N:35]=[CH:34][CH:33]=2)=[CH:30][C:29]([C:38](O)=[O:39])=[CH:28]1.C(N(CC)C(C)C)(C)C.F[P-](F)(F)(F)(F)F.Br[P+](N1CCCC1)(N1CCCC1)N1CCCC1>ClCCl>[O:14]=[C:5]1[C:6]2[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=2)[C:12](=[O:13])[N:4]1[CH2:3][C@@H:2]([NH:1][C:38]([C:29]1[CH:30]=[C:31]([C:32]2[N:36]([CH3:37])[N:35]=[CH:34][CH:33]=2)[N:27]([CH3:26])[CH:28]=1)=[O:39])[CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[C:22]([F:25])([F:23])[F:24]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 578268082-{(2S)-2-amino-3-[2-(trifluoromethyl)phenyl]propyl}-1H-isoindole-1,3(2H)-dioneHCID 581729331-methyl-5-(1-methyl-1H-pyrazol-5-yl)-1H-pyrrole-3-carboxylic acid

Product 1

HCID 58172911N-((1S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-{[2-(trifluoromethyl)phenyl]methyl}ethyl)-1-methyl-5-(1-methyl-1H-pyrazol-5-yl)-1H-pyrrole-3-carboxamideYield 95.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of 2-{(2S)-2-amino-3-[2-(trifluoromethyl)phenyl]propyl}-1H-isoindole-1,3(2H)-dione (200 mg, 0.97 mmol)[prepared according to Preparation 5], 1-methyl-5-(1-methyl-1H-pyrazol-5-yl)-1H-pyrrole-3-carboxylic acid (339 mg, 0.97 mmol) and N,N-diisopropylethylamine (0.85 ml, 4.87 mmol) in dichloromethane (4.873 ml) at 25° C. was added bromo-tris-pyrrolidino-phosphonium hexafluorophosphate (501 mg, 1.07 mmol) in one portion. The solution was stirred at 25° C. for 1 h and was then dry loaded onto silica and purified via column chromatography (silica, 30-70% EtOAc in hexanes) yielding N-((1S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-{[2-(trifluoromethyl)phenyl]methyl}ethyl)-1-methyl-5-(1-methyl-1H-pyrazol-5-yl)-1H-pyrrole-3-carboxamide (522 mg, 0.93 mmol, 95% yield) as a white foam: LCMS (ES) m/e 536 (M+H)+.

Workup

  1. customwas then dry
  2. custompurified via column chromatography (silica, 30-70% EtOAc in hexanes)

Sources & evidence

ORD record
ord-6aa6f7e4d37147c88c082c2fc01a2811
Source dataset
uspto-grants-2013_04
Patent number
US08420690B2

Reaction notes

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