Hydrazine hydrate (1:1) → 5-(5-amino-2-((S)-1-(2-((3bS,4aR)-5,5-difluoro-3-(trifluoro methyl)-3b,4,4a,5-tetrahydro-1H-cyclopropa[3,4]cyclopenta[1,2-c]pyrazol-1-yl)acetamido)-2-(3,5-difluorophenyl)ethyl)pyridin-3-yl)-2-fluorobenzamide

HRID 2170365Notes

Reaction equation

HRID 2170365 reaction equation
[F:1][C:2]1([F:56])[C:6]2[N:7]([CH2:14][C:15]([NH:17][C@H:18]([C:28]3[C:33]([C:34]4[CH:35]=[CH:36][C:37]([F:43])=[C:38]([CH:42]=4)[C:39]([NH2:41])=[O:40])=[CH:32][C:31]([N:44]4C(=O)C5C(=CC=CC=5)C4=O)=[CH:30][N:29]=3)[CH2:19][C:20]3[CH:25]=[C:24]([F:26])[CH:23]=[C:22]([F:27])[CH:21]=3)=[O:16])[N:8]=[C:9]([C:10]([F:13])([F:12])[F:11])[C:5]=2[C@H:4]2[CH2:55][C@@H:3]12.O.NN>C(O)C>[NH2:44][C:31]1[CH:32]=[C:33]([C:34]2[CH:35]=[CH:36][C:37]([F:43])=[C:38]([CH:42]=2)[C:39]([NH2:41])=[O:40])[C:28]([C@@H:18]([NH:17][C:15](=[O:16])[CH2:14][N:7]2[C:6]3[C:2]([F:56])([F:1])[C@@H:3]4[CH2:55][C@@H:4]4[C:5]=3[C:9]([C:10]([F:11])([F:12])[F:13])=[N:8]2)[CH2:19][C:20]2[CH:25]=[C:24]([F:26])[CH:23]=[C:22]([F:27])[CH:21]=2)=[N:29][CH:30]=1

Participants

4

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 902814515-(2-((S)-1-(2-((3bS,4aR)-5,5-difluoro-3-(trifluoromethyl)-3b,4,4a,5-tetrahydro-1H-cyclopropa[3,4]cyclopenta[1,2-c]pyrazol-1-yl)acetamido)-2-(3,5-difluorophenyl)ethyl)-5-(1,3-dioxoisoindolin-2-yl)pyridin-3-yl)-2-fluorobenzamide

Product 1

HCID 902812015-(5-amino-2-((S)-1-(2-((3bS,4aR)-5,5-difluoro-3-(trifluoro methyl)-3b,4,4a,5-tetrahydro-1H-cyclopropa[3,4]cyclopenta[1,2-c]pyrazol-1-yl)acetamido)-2-(3,5-difluorophenyl)ethyl)pyridin-3-yl)-2-fluorobenzamide

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Compound 30K (13 mg, 0.017 mmol) was dissolved in 1 ml of ethanol; 0.01 ml of hydrazine monohydrate was added and stirred at room temperature for 2 hours. The solvent was removed and the residue was purified by RP-HPLC eluting with acetonitrile/H2O (with 0.1% TFA) to afford the title compound. 1H NMR (400 MHz, CD3OD) δ 8.07 (d, 1H), 7.38 (m, 2H), 7.28-7.07 (m, 2H), 6.71 (t, 1H), 6.35 (m, 2H), 5.14 (m, 1H), 4.90 (s, 2H), 3.13 (m, 1H), 3.01-2.91 (m, 1H), 2.48 (m, 2H), 1.40 (m, 1H), 1.09 (m, 1H). MS (m/z) 650.94 [M+H]+.

Workup

  1. customThe solvent was removed
  2. customthe residue was purified by RP-HPLC
  3. washeluting with acetonitrile/H2O (with 0.1% TFA)

Sources & evidence

ORD record
ord-75df13bba59b48fc89bda19e8048fa0c
Source dataset
uspto-grants-2015_06
Patent number
US09050344B2

Reaction notes

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