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

HRID 2392003Notes

Reaction equation

HRID 2392003 reaction equation
O=C1C2C(=CC=CC=2)C(=O)[N:3]1[CH2:12][C@@H:13]([NH:25][C:26]([C:28]1[S:29][CH:30]=[C:31]([C:33]2[N:37]([CH3:38])[N:36]=[CH:35][C:34]=2[F:39])[CH:32]=1)=[O:27])[CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[C:21]([F:24])([F:23])[F:22].NN>C1COCC1.CO>[NH2:3][CH2:12][C@@H:13]([NH:25][C:26]([C:28]1[S:29][CH:30]=[C:31]([C:33]2[N:37]([CH3:38])[N:36]=[CH:35][C:34]=2[F:39])[CH:32]=1)=[O:27])[CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[C:21]([F:24])([F:23])[F:22]

Participants

4

Reactant 2

HCID 9321HydrazineHCID 57826724N-((1S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-{[2-(trifluoromethyl)phenyl]methyl}ethyl)-4-(4-fluoro-1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxamide

Product 1

HCID 24994372N-((1S)-2-amino-1-{[2-(trifluoromethyl)phenyl]methyl}ethyl)-4-(4-fluoro-1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxamide

Reagents, catalysts & solvents 1

HCID 21899815MeOH tetrahydrofuranSolvent

Procedure

To a solution of N-((1S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-{[2-(trifluoromethyl)phenyl]methyl}ethyl)-4-(4-fluoro-1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxamide (135 mg, 0.242 mmol) in THF-MeOH (1:1, 2 mL) was added hydrazine (75 uL, 2.42 mmol). After 12 h, the solution was filtered and the filtrate was concentrated, dry loaded onto silica and purified via column chromatography (3% MeOH in DCM (1% NH4OH)). The title compound was further purified via Gilson reverse phase chromatography using 5-95% mobile phase gradient affording the TFA-salt of the title compound which was neutralized through a silica plug ((5% MeOH in DCM (1% NH4OH)) then transferred to the HCl salt using excess 4M HCl in dioxane (40 mg, 26%): LCMS (ES) m/z 427 (M+H)+, 1H NMR (400 MHz, DMSO-d6) d ppm 8.88 (d, J=8.84 Hz, 1H) 8.13 (s, 1H) 8.06 (bs, 3H) 7.70 (d, J=7.83 Hz, 1H) 7.55-7.62 (m, 3H) 7.54 (br. s., 1H) 7.41 (d, J=2.53 Hz, 1H) 4.49 (d, J=5.05 Hz, 1H) 3.92 (s, 3H) 2.99-3.11 (m, 4H).

Workup

  1. filtrationthe solution was filtered
  2. concentrationthe filtrate was concentrated
  3. customdry loaded onto silica
  4. custompurified via column chromatography (3% MeOH in DCM (1% NH4OH))
  5. customThe title compound was further purified via Gilson

Sources & evidence

ORD record
ord-d16a3d208ef4436eb2054fe04215ffed
Source dataset
uspto-grants-2012_09
Patent number
US08273782B2

Reaction notes

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