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

HRID 2392181Notes

Reaction equation

HRID 2392181 reaction equation
[CH3:1][N:2]1[C:6]([C:7]2[CH:8]=[C:9]([C:13]([OH:15])=O)[S:10][C:11]=2[CH3:12])=[C:5]([CH3:16])[CH:4]=[N:3]1.[NH2:17][C@@H:18]([CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[C:34]([C:38]([F:41])([F:40])[F:39])[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>[CH3:1][N:2]1[C:6]([C:7]2[CH:8]=[C:9]([C:13]([NH:17][C@@H:18]([CH2:31][C:32]3[CH:37]=[CH:36][CH:35]=[C:34]([C:38]([F:41])([F:39])[F:40])[CH:33]=3)[CH2:19][N:20]3[C:21](=[O:30])[C:22]4[C:27](=[CH:26][CH:25]=[CH:24][CH:23]=4)[C:28]3=[O:29])=[O:15])[S:10][C:11]=2[CH3:12])=[C:5]([CH3:16])[CH:4]=[N:3]1

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 2761473Boc-2-(trifluoromethyl)-L-phenylalanineHCID 578266574-(1,4-dimethyl-1H-pyrazol-5-yl)-5-methyl-2-thiophenecarboxylic acidHCID 670660602-{(2S)-2-amino-3-[3-(trifluoromethyl)phenyl]propyl}-1H-isoindole-1,3(2H)-dione

Product 1

HCID 578265484-(1,4-dimethyl-1H-pyrazol-5-yl)-N-((1S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-{[3-(trifluoromethyl)phenyl]methyl}ethyl)-5-methyl-2-thiophenecarboxamideYield 82.1%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To a 50 mL round-bottomed flask was added 4-(1,4-dimethyl-1H-pyrazol-5-yl)-5-methyl-2-thiophenecarboxylic acid (170 mg, 0.68 mmol), 2-{(2S)-2-amino-3-[3-(trifluoromethyl)phenyl]propyl}-1H-isoindole-1,3(2H)-dione (256 mg, 0.67 mmol) [prepared according to the procedure of Preparation 6 except substituting N-{[(1,1-dimethylethyl)oxy]carbonyl}-3-(trifluoromethyl)-L-phenylalanine (4.98 g, 15.0 mmol) for N-{[(1,1-dimethylethyl)oxy]carbonyl}-2-(trifluoromethyl)-L-phenylalanine] and PyBrop (387 mg, 0.83 mmol) in chloroform (7 mL). DIEA (600 μL, 3.44 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 (311 mg, 0.55 mmol, 80%): LC-MS (ES) m/z=567 (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-cba47e64a73b498b8d81db323b8e5fa9
Source dataset
uspto-grants-2012_09
Patent number
US08273782B2

Reaction notes

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