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

HRID 2392087Notes

Reaction equation

HRID 2392087 reaction equation
[CH3:1][C:2]1[S:6][C:5]([C:7]([OH:9])=O)=[CH:4][C:3]=1[C:10]1[N:14]([CH3:15])[N:13]=[CH:12][C:11]=1[CH:16]([CH3:18])[CH3:17].[NH2:19][C@@H:20]([CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=1[C:40]([F:43])([F:42])[F:41])[CH2:21][N:22]1[C:30](=[O:31])[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[C:23]1=[O:32].C(N(C(C)C)CC)(C)C.F[P-](F)(F)(F)(F)F.Br[P+](N1CCCC1)(N1CCCC1)N1CCCC1>C(Cl)Cl>[O:31]=[C:30]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[C:23](=[O:32])[N:22]1[CH2:21][C@@H:20]([NH:19][C:7]([C:5]1[S:6][C:2]([CH3:1])=[C:3]([C:10]2[N:14]([CH3:15])[N:13]=[CH:12][C:11]=2[CH:16]([CH3:18])[CH3:17])[CH:4]=1)=[O:9])[CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=1[C:40]([F:42])([F:41])[F:43]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 578268082-{(2S)-2-amino-3-[2-(trifluoromethyl)phenyl]propyl}-1H-isoindole-1,3(2H)-dioneHCID 578268425-methyl-4-[1-methyl-4-(1-methylethyl)-1H-pyrazol-5-yl]-2-thiophenecarboxylic acid

Product 1

HCID 57826580N-((1S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-{[2-(trifluoromethyl)phenyl]methyl}ethyl)-5-methyl-4-[1-methyl-4-(1-methylethyl)-1H-pyrazol-5-yl]-2-thiophenecarboxamideYield 64.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of 5-methyl-4-[1-methyl-4-(1-methylethyl)-1H-pyrazol-5-yl]-2-thiophenecarboxylic acid (137 mg, 0.52 mmol), 2-{(2S)-2-amino-3-[2-(trifluoromethyl)phenyl]propyl}-1H-isoindole-1,3(2H)-dione (200 mg, 0.52 mmol) [Prepared in Preparation 6] and diisopropylethylamine (0.45 ml, 2.60 mmol) in DCM at 25° C. was added bromo-tris-pyrrolidino-phosphonium hexafluorophosphate (267 mg, 0.572 mmol) in one portion. The solution stirred at 25° C. for 12 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)-5-methyl-4-[1-methyl-4-(1-methylethyl)-1H-pyrazol-5-yl]-2-thiophenecarboxamide (211 mg, 0.334 mmol, 64.2% yield) as a yellow oil: LCMS (ES) m/e 595 (M+H)+.

Workup

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

Sources & evidence

ORD record
ord-6d56834efd164825a4995bab4ff36c03
Source dataset
uspto-grants-2012_09
Patent number
US08273782B2

Reaction notes

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