Hydrazine → N-((1S)-2-amino-1-{[2-(trifluoromethyl)phenyl]methyl}ethyl)-2-chloro-1-methyl-5-(1-methyl-1H-pyrazol-5-yl)-1H-pyrrole-3-carboxamide

HRID 1967120Notes

Reaction equation

HRID 1967120 reaction equation
[Cl:1][C:2]1[N:3]([CH3:40])[C:4]([C:34]2[N:38]([CH3:39])[N:37]=[CH:36][CH:35]=2)=[CH:5][C:6]=1[C:7]([NH:9][C@@H:10]([CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[C:30]([F:33])([F:32])[F:31])[CH2:11][N:12]1C(=O)C2C(=CC=CC=2)C1=O)=[O:8].NN>O1CCCC1.CO>[NH2:12][CH2:11][C@@H:10]([NH:9][C:7]([C:6]1[CH:5]=[C:4]([C:34]2[N:38]([CH3:39])[N:37]=[CH:36][CH:35]=2)[N:3]([CH3:40])[C:2]=1[Cl:1])=[O:8])[CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[C:30]([F:33])([F:32])[F:31]

Participants

5

Reactant 2

HCID 9321HydrazineHCID 581729142-chloro-N-((1S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-{[2-(trifluoromethyl)phenyl]methyl}ethyl)-1-methyl-5-(1-methyl-1H-pyrazol-5-yl)-1H-pyrrole-3-carboxamide

Product 1

HCID 24997128N-((1S)-2-amino-1-{[2-(trifluoromethyl)phenyl]methyl}ethyl)-2-chloro-1-methyl-5-(1-methyl-1H-pyrazol-5-yl)-1H-pyrrole-3-carboxamideYield 59.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-chloro-N-((1S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-{[2-(trifluoromethyl)phenyl]methyl}ethyl)-1-methyl-5-(1-methyl-1H-pyrazol-5-yl)-1H-pyrrole-3-carboxamide (125 mg, 0.22 mmol) in tetrahydrofuran (1.1 ml) and methanol (1.1 ml) at 25° C. was added hydrazine (0.06 ml, 1.76 mmol) dropwise. After 12 h the solution was concentrated, dry loaded onto silica and purified by column chromatography (2% MeOH in DCM (1% NH4OH)). The free base was transferred to the HCl salt by addition of excess 2M HCl in Ether (20 ml) to the residue in DCM (40 ml) affording the HCl salt of N-((1S)-2-amino-1-{[2-(trifluoromethyl)phenyl]methyl}ethyl)-2-chloro-1-methyl-5-(1-methyl-1H-pyrazol-5-yl)-1H-pyrrole-3-carboxamide (70 mg, 0.13 mmol, 57% yield) as a white solid: LCMS (ES) m/z=440, 442 (M, M+2)+, 1H NMR (400 MHz, DMSO-d6) δ ppm 8.17 (d, J=9.09 Hz, 1 H) 8.08 (br. s., 2 H) 7.69 (d, J=8.08 Hz, 1 H) 7.58 (br. s., 1 H) 7.57 (d, J=2.02 Hz, 1 H) 7.40-7.43 (m, 1 H) 7.02 (s, 1 H) 6.48 (d, J=2.02 Hz, 1 H) 4.50-4.57 (m, 1 H) 3.78 (s, 3 H) 3.44 (s, 3 H) 2.98-3.07 (m, 4 H).

Workup

  1. concentrationAfter 12 h the solution was concentrated
  2. customdry loaded onto silica
  3. custompurified by column chromatography (2% MeOH in DCM (1% NH4OH))
  4. additionThe free base was transferred to the HCl salt by addition of excess 2M HCl in Ether (20 ml) to the residue in DCM (40 ml)

Sources & evidence

ORD record
ord-8312680d4ef44d21ab53d54665437948
Source dataset
uspto-grants-2013_04
Patent number
US08420690B2

Reaction notes

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