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-1H-pyrazol-5-yl)-2-furancarboxamide

HRID 1961139Notes

Reaction equation

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

Participants

Conditions

Temperature: 25 °C

Procedure

To a solution of 5-methyl-4-(1-methyl-1H-pyrazol-5-yl)-2-furancarboxylic acid (130 mg, 0.63 mmol), 2-{(2S)-2-amino-3-[2-(trifluoromethyl)phenyl]propyl}-1H-isoindole-1,3(2H)-dione (243 mg, 0.63 mmol)[prepared in Preparation 6] and diisopropylethylamine (0.55 ml, 3.15 mmol) in DCM at 25° C. was added bromo-tris-pyrrolidino-phosphonium hexafluorophosphate (324 mg, 0.69 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-1H-pyrazol-5-yl)-2-furancarboxamide (190 mg, 0.23 mmol, 37% yield) as a clear oil: LCMS (ES) m/e 537 (M+H)+.

Workup

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

Sources & evidence

ORD record: ord-7d3b86998a424b00a99fc27f4c6c6d10
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08410158B2

Reaction notes

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