Hydrazine → N-{(1S)-2-amino-1-[(3-fluorophenyl)methyl]ethyl}-5-chloro-4-(1-ethyl-4-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxamide

HRID 1845666Notes

Reaction equation

HRID 1845666 reaction equation
NN.[Cl:3][C:4]1[S:8][C:7]([C:9]([NH:11][C@@H:12]([CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([F:32])[CH:27]=2)[CH2:13][N:14]2C(=O)C3C(=CC=CC=3)C2=O)=[O:10])=[CH:6][C:5]=1[C:33]1[N:37]([CH2:38][CH3:39])[N:36]=[CH:35][C:34]=1[CH3:40]>CO>[NH2:14][CH2:13][C@@H:12]([NH:11][C:9]([C:7]1[S:8][C:4]([Cl:3])=[C:5]([C:33]2[N:37]([CH2:38][CH3:39])[N:36]=[CH:35][C:34]=2[CH3:40])[CH:6]=1)=[O:10])[CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([F:32])[CH:27]=1

Participants

4

Reactant 2

HCID 9321HydrazineHCID 578266125-chloro-N-{(1S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-[(3-fluorophenyl)methyl]ethyl}-4-(1-ethyl-4-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxamide

Product 1

HCID 57826583N-{(1S)-2-amino-1-[(3-fluorophenyl)methyl]ethyl}-5-chloro-4-(1-ethyl-4-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxamideYield 66.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

At RT, NH2NH2 (0.1 mL, 3.19 mmol) was added to 5-chloro-N-{(1S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-[(3-fluorophenyl)methyl]ethyl}-4-(1-ethyl-4-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxamide (201 mg, 0.36 mmol) in MeOH (3 mL). After 10 h, the solvent was removed under vacuum. The resulting residue was taken into DCM (10 mL) and washed with H2O (10 mL×3). To the DCM solution was added HCl (36%, 2 mL). After 1 h, the aqueous phase was separated and washed with DCM (10 ml×3). Water was removed under high vacuum to give the title compound (101 mg, 53%) as an off-white solid: LC-MS (ES) m/z 421 (M+H)+, 1H NMR (d6-DMSO, 400 MHz) δ ppm 9.02 (d, J=8.3 Hz, 1H), 8.08 (s, 2H), 7.97 (s, 1H), 7.42 (s, 1H), 7.32 (m, 1H), 7.15-7.09 (m, 1H), 7.06-7.01 (m, 1H), 4.35 (m, 1H), 3.95 (m, 2H), 3.05-2.98 (m, 2H), 2.96-2.88 (m, 2H), and 1.92 (s, 3H), and 1.24 (t, J=6.6 Hz, 3H).

Workup

  1. customthe solvent was removed under vacuum
  2. washwashed with H2O (10 mL×3)
  3. additionTo the DCM solution was added HCl (36%, 2 mL)
  4. waitAfter 1 h
  5. customthe aqueous phase was separated
  6. washwashed with DCM (10 ml×3)
  7. customWater was removed under high vacuum

Sources & evidence

ORD record
ord-fe8da40ba1524c11b169016847d09adc
Source dataset
uspto-grants-2015_02
Patent number
US08946278B2

Reaction notes

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