Hydrazine → N-((1S)-2-amino-1-{[2-(trifluoromethyl)phenyl]methyl}ethyl)-4-(4-chloro-1-ethyl-1H-pyrazol-5-yl)-2-thiophenecarboxamide

HRID 1961056Notes

Reaction equation

HRID 1961056 reaction equation
[Cl:1][C:2]1[CH:3]=[N:4][N:5]([CH2:39][CH3:40])[C:6]=1[C:7]1[CH:8]=[C:9]([C:12]([NH:14][C@@H:15]([CH2:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=2[C:35]([F:38])([F:37])[F:36])[CH2:16][N:17]2C(=O)C3C(=CC=CC=3)C2=O)=[O:13])[S:10][CH:11]=1.NN>CO>[NH2:17][CH2:16][C@@H:15]([NH:14][C:12]([C:9]1[S:10][CH:11]=[C:7]([C:6]2[N:5]([CH2:39][CH3:40])[N:4]=[CH:3][C:2]=2[Cl:1])[CH:8]=1)=[O:13])[CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[C:35]([F:38])([F:37])[F:36]

Participants

4

Reactant 2

HCID 9321HydrazineHCID 578264884-(4-chloro-1-ethyl-1H-pyrazol-5-yl)-N-((1S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-{[2-(trifluoromethyl)phenyl]methyl}ethyl)-2-thiophenecarboxamide

Product 1

HCID 57826598N-((1S)-2-amino-1-{[2-(trifluoromethyl)phenyl]methyl}ethyl)-4-(4-chloro-1-ethyl-1H-pyrazol-5-yl)-2-thiophenecarboxamide

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

4-(4-chloro-1-ethyl-1H-pyrazol-5-yl)-N-((1S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-{[2-(trifluoromethyl)phenyl]methyl}ethyl)-2-thiophenecarboxamide (350 mg, 0.60 mmol) was dissolved in MeOH (5 mL) and treated with NH2NH2 (0.5 mL, 15.93 mmol). The mixture was stirred at RT overnight, and concentrated. The residue was purified by column chromatography (silica, 2-5% MeOH in CHCl3 (0.5% NH4OH) affording the free base of the title compound, which was treated with HCl(aq) in MeOH to give title compound (0.16 g, 51%) as a off white solid: LC-MS (ES) m/z=457 (M+H)+. 1H NMR (d4-MeOD, 400 MHz) δ ppm 7.97-7.94 (m, 2H), 7.71 (d, J=7.8 Hz, 1H), 7.61 (s, 1H), 7.56-7.51 (m, 2H), 7.43 (dd, J=7.6, 7.6 Hz, 1H), 4.67 (m, 1H), 4.22 (q, J=7.1 Hz, 2H), 3.36-3.12 (m, 4H), and 1.38 (t, J=7.1 Hz, 3H).

Workup

  1. concentrationconcentrated
  2. customThe residue was purified by column chromatography (silica, 2-5% MeOH in CHCl3 (0.5% NH4OH)

Sources & evidence

ORD record
ord-0012b7ca128a41299191971c4f1bbe0f
Source dataset
uspto-grants-2013_04
Patent number
US08410158B2

Reaction notes

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