Hydrazine hydrate (1:1) → 3,5-diamino-N-(5-fluoro-4-(4-(4-methylpiperazine-1-carbonyl)piperidin-1-yl)pyridin-3-yl)-1H-pyrazole-4-carboxamide

HRID 524849Notes

Reaction equation

HRID 524849 reaction equation
[NH2:1][C:2](C(Cl)(Cl)Cl)=[C:3]([C:29]#[N:30])[C:4]([NH:6][C:7]1[CH:8]=[N:9][CH:10]=[C:11]([F:28])[C:12]=1[N:13]1[CH2:18][CH2:17][CH:16]([C:19]([N:21]2[CH2:26][CH2:25][N:24]([CH3:27])[CH2:23][CH2:22]2)=[O:20])[CH2:15][CH2:14]1)=O.[OH2:35].[NH2:36][NH2:37]>CN1CCCC1=O>[NH2:1][C:2]1[C:3]([C:4]([NH:6][C:7]2[CH:8]=[N:9][CH:10]=[C:11]([F:28])[C:12]=2[N:13]2[CH2:14][CH2:15][CH:16]([C:19]([N:21]3[CH2:22][CH2:23][N:24]([CH3:27])[CH2:25][CH2:26]3)=[O:20])[CH2:17][CH2:18]2)=[O:35])=[C:29]([NH2:30])[NH:37][N:36]=1

Participants

4

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 867209073-Amino-4,4,4-trichloro-2-cyano-N-[5-fluoro-4-[4-(4-methylpiperazine-1-carbonyl)-1-piperidyl]-3-pyridyl]but-2-enamide

Product 1

HCID 867209063,5-diamino-N-(5-fluoro-4-(4-(4-methylpiperazine-1-carbonyl)piperidin-1-yl)pyridin-3-yl)-1H-pyrazole-4-carboxamide

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

3-Amino-4,4,4-trichloro-2-cyano-N-[5-fluoro-4-[4-(4-methylpiperazine-1-carbonyl)-1-piperidyl]-3-pyridyl]but-2-enamide (4.1 g, 7.695 mmol) was dissolved in N-methylpyrrolidinone (40 mL). Hydrazine hydrate (1.002 g, 973.8 μL, 20.01 mmol) was added and the reaction mixture was stirred at room temperature for 10 mins, then heated at 80° C. for 3.5 h. The mixture was concentrated in vacuo and the residue was then partitioned between EtOAc/water. The organic layer was washed with water (2×), brine (1×), dried (MgSO4), filtered and concentrated in vacuo to provide the desired compound as a white solid. (64%). MS (ES+) 446.1, 1H NMR (500 MHz, DMSO) 11.03 (s, 1H), 9.45 (s, 1H), 8.69 (s, 1H), 8.52 (d, J=4.7 Hz, 1H), 7.36 (br s, 4H), 4.47-4.43 (m, 1H), 4.23-4.21 (m, 1H), 3.50-3.47 (m, 2H), 3.41-3.39 (m, 2H), 3.24-3.15 (m, 2H) 3.05-2.98 (m, 2H), 2.93-2.88 (m, 2H), 2.77-2.76 (m, 4H), 1.73-1.71 (m, 4H).

Workup

  1. temperatureheated at 80° C. for 3.5 h
  2. concentrationThe mixture was concentrated in vacuo
  3. customthe residue was then partitioned between EtOAc/water
  4. washThe organic layer was washed with water (2×), brine (1×)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-d01df9c326204ab4b795c9f8a082d55d
Source dataset
uspto-grants-2016_05
Patent number
US09340546B2

Reaction notes

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