Hydrazine → HCID 24992140, compound

HRID 1961125Notes

Reaction equation

HRID 1961125 reaction equation
[Cl:1][C:2]1[CH:3]=[N:4][N:5]([CH3:42])[C:6]=1[C:7]1[CH:8]=[C:9]([C:15]([NH:17][C@@H:18]([CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=2[C:38]([F:41])([F:40])[F:39])[CH2:19][N:20]2C(=O)C3C(=CC=CC=3)C2=O)=[O:16])[S:10][C:11]=1[CH2:12][CH2:13][CH3:14].NN>O1CCCC1.CO>[NH2:20][CH2:19][C@@H:18]([NH:17][C:15]([C:9]1[S:10][C:11]([CH2:12][CH2:13][CH3:14])=[C:7]([C:6]2[N:5]([CH3:42])[N:4]=[CH:3][C:2]=2[Cl:1])[CH:8]=1)=[O:16])[CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=1[C:38]([F:41])([F:40])[F:39]

Participants

5

Reactant 2

HCID 9321HydrazineHCID 57826910HCID 57826910, compound

Product 1

HCID 24992140HCID 24992140, compoundYield 80%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-N-((1S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-{[2-(trifluoromethyl)phenyl]methyl}ethyl)-5-propyl-2-thiophenecarboxamide (245 mg, 0.40 mmol) in tetrahydrofuran (2.4 ml) and methanol (2.4 ml) at 25° C. was added hydrazine (0.12 ml, 3.98 mmol) dropwise. After 12 h, the solution was concentrated, dry loaded onto silica and purified by column chromatography (5% MeOH in DCM (1% NH4OH)). The free base was transferred to the HCl salt by addition of excess 4M HCl in dioxane (1 ml) to the residue in MeOH (2 ml) affording the HCl salt of N-((1S)-2-amino-1-{[2-(trifluoromethyl)phenyl]methyl}ethyl)-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-5-propyl-2-thiophenecarboxamide (178 mg, 0.32 mmol, 80% yield) as a yellow solid: LCMS (ES) m/z=485, 487 (M, M+2)+, 1H NMR (400 MHz, DMSO-d6) δ ppm 8.96 (br. s., 1H) 8.13 (br. s., 3H) 7.93 (s, 1H) 7.66-7.73 (m, 2H) 7.62 (br. s., 1H) 7.55 (t, J=7.45 Hz, 1H) 7.42 (t, J=7.45 Hz, 1H) 4.48 (br. s., 1H) 3.71 (s, 3H) 2.99-3.08 (m, 4H) 2.63 (t, J=7.20 Hz, 2H) 1.53-1.57 (m, 2H) 0.83 (t, J=7.33 Hz, 3H).

Workup

  1. concentrationthe solution was concentrated
  2. customdry loaded onto silica
  3. custompurified by column chromatography (5% MeOH in DCM (1% NH4OH))
  4. additionThe free base was transferred to the HCl salt by addition of excess 4M HCl in dioxane (1 ml) to the residue in MeOH (2 ml)

Sources & evidence

ORD record
ord-1603c552f1524014b803ac7c9ffe8389
Source dataset
uspto-grants-2013_04
Patent number
US08410158B2

Reaction notes

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