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

HRID 1961067
Notes
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Reaction equation

HRID 1961067 reaction equation
[Cl: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][CH:11]=1.[NH2:16][C@@H:17]([CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([F:37])[CH:32]=1)[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.C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>ClCCl>[Cl:1][C:2]1[S:6][C:5]([C:7]([NH:16][C@@H:17]([CH2:30][C:31]2[CH:36]=[CH:35][CH:34]=[C:33]([F:37])[CH:32]=2)[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])=[O:9])=[CH:4][C:3]=1[C:10]1[N:14]([CH3:15])[N:13]=[CH:12][CH:11]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 578263895-chloro-4-(1-methyl-1H-pyrazol-5-yl)thiophene-2-carboxylic acidHCID 58226866(S)-2-(2-amino-3-(3-fluorophenyl)propyl)isoindoline-1,3-dione

Product 1

HCID 578266985-chloro-N-{(1S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-[(3-fluorophenyl)methyl]ethyl}-4-(1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a 500 mL round-bottomed flask was added 5-chloro-4-(1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxylic acid (4.2 g, 17.31 mmol), 2-[(2S)-2-amino-3-(3-fluorophenyl)propyl]-1H-isoindole-1,3(2H)-dione (6.37 g, 19.04 mmol) [prepared according to the procedure of Preparation 6], N,N-diisopropyl ethylamine (4.53 ml, 26.0 mmol) and Pybrop (12.05 g, 26.0 mmol) in dichloromethane (DCM) (150 ml). After stirring at RT for 12 h, the reaction solution was washed with H2O (2×100 mL) and the organic layer was dried Na2SO4, filtered and concentrated. The crude product was added to a silica gel column and was eluted with [EtOAc/hexanes, 1:1] to give the product [7.8 g, 86%] as a white solid: LCMS (ES) m/z 524 (M+H)+.

Workup

  1. customprepared
  2. washthe reaction solution was washed with H2O (2×100 mL)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. additionThe crude product was added to a silica gel column
  6. washwas eluted with [EtOAc/hexanes, 1:1]
  7. customto give the product [7.8 g, 86%] as a white solid

Sources & evidence

ORD record
ord-3226a58c190944099bbbec517e387713
Source dataset
uspto-grants-2013_04
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08410158B2

Reaction notes

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