Acetic Acid → 2-amino-6-fluoro-N-(5-fluoro-4-(4-(4-methylpiperazine-1-carbonyl)piperidin-1-yl)pyridin-3-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide

HRID 524850Notes

Reaction equation

HRID 524850 reaction equation
[NH2:1][C:2]1[C:6]([C:7]([NH:9][C:10]2[CH:11]=[N:12][CH:13]=[C:14]([F:31])[C:15]=2[N:16]2[CH2:21][CH2:20][CH:19]([C:22]([N:24]3[CH2:29][CH2:28][N:27]([CH3:30])[CH2:26][CH2:25]3)=[O:23])[CH2:18][CH2:17]2)=[O:8])=[C:5]([NH2:32])[NH:4][N:3]=1.C(O)(=O)C.C(N(C(C)C)[CH:41]=[C:42]([F:45])[CH:43]=O)(C)C>CC(O)C.O.C(O)C>[NH2:32][C:5]1[C:6]([C:7]([NH:9][C:10]2[CH:11]=[N:12][CH:13]=[C:14]([F:31])[C:15]=2[N:16]2[CH2:17][CH2:18][CH:19]([C:22]([N:24]3[CH2:25][CH2:26][N:27]([CH3:30])[CH2:28][CH2:29]3)=[O:23])[CH2:20][CH2:21]2)=[O:8])=[C:2]2[N:1]=[CH:41][C:42]([F:45])=[CH:43][N:3]2[N:4]=1

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 727413933-(Diisopropylamino)-2-fluoro-prop-2-enalHCID 867209063,5-diamino-N-(5-fluoro-4-(4-(4-methylpiperazine-1-carbonyl)piperidin-1-yl)pyridin-3-yl)-1H-pyrazole-4-carboxamide

Product 1

HCID 867209012-amino-6-fluoro-N-(5-fluoro-4-(4-(4-methylpiperazine-1-carbonyl)piperidin-1-yl)pyridin-3-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 21889133Propan-2-ol--water (1/1)Solvent

Procedure

To a suspension of 3,5-diamino-N-[5-fluoro-4-[4-(4-methylpiperazine-1-carbonyl)-1-piperidyl]-3-pyridyl]-1H-pyrazole-4-carboxamide 9a (106 mg, 1.19 mmol) in IPA/water (1:1, 1 mL) and acetic acid (71.46 mg, 67.67 μL, 0.1078 mmol) was added 3-(diisopropylamino)-2-fluoro-prop-2-enal (41.21 mg, 0.2379 mmol). The reaction mixture was heated under reflux for 6 h and was then allowed to cool to room temperature overnight. IPA was removed in vacuo, and the resulting aqueous solution was partitioned between DCM and 2M sodium carbonate solution. The organic layer was washed with 1:1 brine/water, dried (MgSO4) filtered and concentrated in vacuo to leave a yellow solid which was stirred as a suspension in ethanol (0.5 mL) for 2 h. The solid was collected by filtration to give the desired compound I-G-4 (63 mg, 53%).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureunder reflux for 6 h
  3. customIPA was removed in vacuo
  4. customthe resulting aqueous solution was partitioned between DCM and 2M sodium carbonate solution
  5. washThe organic layer was washed with 1:1 brine/water
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto leave a yellow solid which
  10. filtrationThe solid was collected by filtration

Sources & evidence

ORD record
ord-3f1efe1f0c874fd78e781a6ec231322a
Source dataset
uspto-grants-2016_05
Patent number
US09340546B2

Reaction notes

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