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

HRID 1961283Notes

Reaction equation

HRID 1961283 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[Cl: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[Cl: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 578267365-chloro-4-(4-chloro-1-ethyl-1H-pyrazol-5-yl)-N-{(1S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-[(3-fluorophenyl)methyl]ethyl}-2-thiophenecarboxamide

Product 1

HCID 57826584N-{(1S)-2-amino-1-[(3-fluorophenyl)methyl]ethyl}-5-chloro-4-(4-chloro-1-ethyl-1H-pyrazol-5-yl)-2-thiophenecarboxamideYield 82.8%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

At RT, NH2NH2 (0.15 ml, 4.78 mmol) was added to 5-chloro-4-(4-chloro-1-ethyl-1H-pyrazol-5-yl)-N-{(1S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-[(3-fluorophenyl)methyl]ethyl}-2-thiophenecarboxamide (280 mg, 0.49 mmol) in MeOH (5 mL). After 10 h the solvent was removed under vacuum. The resulting residue was dissolved in DCM (15 mL), and washed with H2O (10 mL×3). To the DCM solution was added HCl (12 N, 1.0 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 tilte compound (179 mg, 67.5%) as an off-white solid: LC-MS (ES) m/z=441 (M+H)+, 1H NMR (d4-MeOD, 400 MHz) δ ppm 7.72-7.67 (m, 1H), 7.62 (s, 1H), 7.35-7.29 (m, 1H), 7.14-7.17 (m, 2H), 7.00-6.96 (m, 1H), 4.53 (m, 1H), 4.14-3.97 (m, 2H), 3.37-3.15 (m, 2H), 3.07-2.97 (m, 2H), and 1.33 (t, J=7.1 Hz, 3H).

Workup

  1. customAfter 10 h the solvent was removed under vacuum
  2. dissolutionThe resulting residue was dissolved in DCM (15 mL)
  3. washwashed with H2O (10 mL×3)
  4. additionTo the DCM solution was added HCl (12 N, 1.0 mL)
  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-bc5ad582244c40fcb9b30675bd2ed231
Source dataset
uspto-grants-2013_04
Patent number
US08410158B2

Reaction notes

Loading…