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

HRID 1961276Notes

Reaction equation

HRID 1961276 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][C:34]([F:37])=[CH:33][C:32]=1F)[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(CC)C(C)C)(C)C.[F:48][P-](F)(F)(F)(F)F.Br[P+](N1CCCC1)(N1CCCC1)N1CCCC1>C(Cl)Cl>[F:48][C:33]1[CH:32]=[C:31]([CH2:30][C@H:17]([NH:16][C:7]([C:5]2[O:6][C:2]([CH3:1])=[C:3]([C:10]3[N:14]([CH3:15])[N:13]=[CH:12][CH:11]=3)[CH:4]=2)=[O:9])[CH2:18][N:19]2[C:27](=[O:28])[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[C:20]2=[O:29])[CH:36]=[CH:35][C:34]=1[F:37]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 578265645-methyl-4-(1-methyl-1H-pyrazol-5-yl)-2-furancarboxylic acidHCID 670663202-[(2S)-2-amino-3-(2,4-difluorophenyl)propyl]-1H-isoindole-1,3(2H)-dione

Product 1

HCID 57826789N-{(1S)-2-(3,4-difluorophenyl)-1-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]ethyl}-5-methyl-4-(1-methyl-1H-pyrazol-5-yl)-2-furancarboxamideYield 37.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 5-methyl-4-(1-methyl-1H-pyrazol-5-yl)-2-furancarboxylic acid (200 mg, 0.97 mmol), 2-[(2S)-2-amino-3-(2,4-difluorophenyl)propyl]-1H-isoindole-1,3(2H)-dione (322 mg, 1.02 mmol)[prepared according to the procedure of Preparation 6] and N,N-diisopropylethylamine (0.51 ml, 2.91 mmol) in DCM (10 ml) was added bromo-tris-pyrrolidino-phosphonium hexafluorophosphate (678 mg, 1.46 mmol). After stirring at ambient temperature for 20 h, the mixture was concentrated and purified using silica gel and eluting with a 0-50% ethyl acetate/hexane gradient to afford the title compound as an off-white foamy solid (181 mg, 0.36 mmol, 37% yield): LCMS (ES) m/e 505 (M+H)+.

Workup

  1. concentrationthe mixture was concentrated
  2. custompurified
  3. washeluting with a 0-50% ethyl acetate/hexane gradient

Sources & evidence

ORD record
ord-ef528521a4dc415db7566379b4dcdf6d
Source dataset
uspto-grants-2013_04
Patent number
US08410158B2

Reaction notes

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