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

HRID 2392263Notes

Reaction equation

HRID 2392263 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-40bbf53ba1374ca2aa4afe2bd180f268
Source dataset
uspto-grants-2012_09
Patent number
US08273782B2

Reaction notes

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