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

HRID 1845600Notes

Reaction equation

HRID 1845600 reaction equation
[Cl:1][C:2]1[C:6]([CH3:7])=[C:5]([C:8]2[CH:9]=[C:10]([C:13]([OH:15])=O)[S:11][CH:12]=2)[N:4]([CH3:16])[N:3]=1.[NH2:17][C@@H:18]([CH2:31][C:32]1[CH:37]=[CH:36][C:35]([F:38])=[CH:34][CH:33]=1)[CH2:19][N:20]1[C:28](=[O:29])[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[C:21]1=[O:30].CC(OC(N[C@H](C(O)=O)CC1C=CC=CC=1C(F)(F)F)=O)(C)C.C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C(Cl)(Cl)Cl>[Cl:1][C:2]1[C:6]([CH3:7])=[C:5]([C:8]2[CH:9]=[C:10]([C:13]([NH:17][C@@H:18]([CH2:31][C:32]3[CH:33]=[CH:34][C:35]([F:38])=[CH:36][CH:37]=3)[CH2:19][N:20]3[C:28](=[O:29])[C:27]4[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=4)[C:21]3=[O:30])=[O:15])[S:11][CH:12]=2)[N:4]([CH3:16])[N:3]=1

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 2761473Boc-2-(trifluoromethyl)-L-phenylalanineHCID 578264594-(3-chloro-1,4-dimethyl-1H-pyrazol-5-yl)-2-thiophenecarboxylic AcidHCID 670661152-[(2S)-2-amino-3-(4-fluorophenyl)propyl]-1H-isoindole-1,3(2H)-dione

Product 1

HCID 578267844-(3-chloro-1,4-dimethyl-1H-pyrazol-5-yl)-N-{(1S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-[(4-fluorophenyl)methyl]ethyl}-2-thiophenecarboxamideYield 81%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To a 50 mL round-bottomed flask was added 4-(3-chloro-1,4-dimethyl-1H-pyrazol-5-yl)-2-thiophenecarboxylic acid (294 mg, 1.14 mmol), 2-[(2S)-2-amino-3-(4-fluorophenyl)propyl]-1H-isoindole-1,3(2H)-dione (409 mg, 1.22 mmol) [prepared according to the procedure of Preparation 6 except substituting N-{[(1,1-dimethylethyl)oxy]carbonyl}-4-fluoro-L-phenylalanine (4.95 g, 17.5 mmol) for N-{[(1,1-dimethylethyl)oxy]carbonyl}-2-(trifluoromethyl)-L-phenylalanine] and PyBrop (645 mg, 1.38 mmol) in chloroform (10 mL). DIEA (1 mL, 5.73 mmol) was added and the reaction stirred overnight at room temperature. The mixture was adsorbed onto silica and purified via column chromatography (25-70% EtOAc/Hex) affording the title compound (534 mg, 0.92 mmol, 81%): LC-MS (ES) m/z=537 (M+H)+.

Workup

  1. customprepared
  2. customaccording to the procedure of Preparation 6
  3. custompurified via column chromatography (25-70% EtOAc/Hex)

Sources & evidence

ORD record
ord-716c7d6a52bf4524b97c05bc9a4fb0c9
Source dataset
uspto-grants-2015_02
Patent number
US08946278B2

Reaction notes

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