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

HRID 2392111Notes

Reaction equation

HRID 2392111 reaction equation
[Cl:1][C:2]1[CH:3]=[N:4][N:5]([CH3:40])[C:6]=1[C:7]1[CH:8]=[C:9]([C:13]([NH:15][C@@H:16]([CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=2[C:36]([F:39])([F:38])[F:37])[CH2:17][N:18]2C(=O)C3C(=CC=CC=3)C2=O)=[O:14])[O:10][C:11]=1[CH3:12].NN>O1CCCC1.CO>[NH2:18][CH2:17][C@@H:16]([NH:15][C:13]([C:9]1[O:10][C:11]([CH3:12])=[C:7]([C:6]2[N:5]([CH3:40])[N:4]=[CH:3][C:2]=2[Cl:1])[CH:8]=1)=[O:14])[CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=1[C:36]([F:39])([F:38])[F:37]

Participants

5

Reactant 2

HCID 9321HydrazineHCID 578268114-(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-methyl-2-furancarboxamide

Product 1

HCID 57826556N-((1S)-2-amino-1-{[2-(trifluoromethyl)phenyl]methyl}ethyl)-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-5-methyl-2-furancarboxamideYield 56%

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-methyl-2-furancarboxamide (246 mg, 0.43 mmol) in tetrahydrofuran (2.1 ml) and methanol (2.1 ml) at 25° C. was added hydrazine (135 μl, 4.31 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 converted 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-methyl-2-furancarboxamide (125 mg, 0.24 mmol, 56% yield) as a yellow solid: LCMS (ES) m/z=441, 443 (M, M+2)+, 1H NMR (400 MHz, DMSO-d6) δ ppm 8.63 (d, J=9.09 Hz, 1H) 8.04 (br. s., 3H) 7.65-7.72 (m, 2H) 7.59 (d, J=7.33 Hz, 1H) 7.57 (br. s., 1H) 7.39-7.47 (m, 1H) 7.29-7.37 (m, 1H) 4.54 (br. s., 1H) 3.73 (s, 3H) 2.98-3.09 (m, 4H) 2.33 (s, 3H).

Workup

  1. concentrationAfter 12 h the solution was concentrated
  2. customdry loaded onto silica
  3. custompurified by column chromatography (5% MeOH in DCM (1% NH4OH))
  4. additionThe free base was converted 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-74ffa4d40a4b4bf6bdbd24c1c81248f8
Source dataset
uspto-grants-2012_09
Patent number
US08273782B2

Reaction notes

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