Hydrazine → methyl 5-((R)-2-(1-((R)-3-amino-2-methylpropyl)-5-fluoro-2-oxo-1,2-dihydropyridin-3-yl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylate

HRID 1426973Notes

Reaction equation

HRID 1426973 reaction equation
O=C1C2C(=CC=CC=2)C(=O)[N:3]1[CH2:12][C@@H:13]([CH3:41])[CH2:14][N:15]1[CH:20]=[C:19]([F:21])[CH:18]=[C:17]([C@H:22]2[CH2:26][CH2:25][CH2:24][N:23]2[C:27]2[CH:32]=[CH:31][N:30]3[N:33]=[CH:34][C:35]([C:36]([O:38][CH3:39])=[O:37])=[C:29]3[N:28]=2)[C:16]1=[O:40].NN>CO.C1COCC1>[NH2:3][CH2:12][C@@H:13]([CH3:41])[CH2:14][N:15]1[CH:20]=[C:19]([F:21])[CH:18]=[C:17]([C@H:22]2[CH2:26][CH2:25][CH2:24][N:23]2[C:27]2[CH:32]=[CH:31][N:30]3[N:33]=[CH:34][C:35]([C:36]([O:38][CH3:39])=[O:37])=[C:29]3[N:28]=2)[C:16]1=[O:40]

Participants

4

Reactant 2

HCID 9321HydrazineHCID 67471119methyl 5-((R)-2-(1-((S)-3-(1,3-dioxoisoindolin-2-yl)-2-methylpropyl)-5-fluoro-2-oxo-1,2-dihydropyridin-3-yl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylate

Product 1

HCID 67471049methyl 5-((R)-2-(1-((R)-3-amino-2-methylpropyl)-5-fluoro-2-oxo-1,2-dihydropyridin-3-yl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylateYield 77%

Reagents, catalysts & solvents 1

HCID 21899815MeOH tetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of methyl 5-((R)-2-(1-((S)-3-(1,3-dioxoisoindolin-2-yl)-2-methylpropyl)-5-fluoro-2-oxo-1,2-dihydropyridin-3-yl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylate (110 mg, 0.197 mmol) in MeOH/THF (3 mL/3 mL) was added hydrazine (31.6 mg, 0.985 mmol). The reaction was stirred for 14 hours at 50° C. After cooling, the reaction mixture was concentrated and the resulting residue was diluted with EtOAc (20 mL) and washed with saturated aqueous NaHCO3 (5 mL), water (2×5 mL) and brine (5 mL). The organic layer was dried with Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by silica column chromatography, eluting with EtOAc/MeOH/NH4OH 10:1:0.1 to give the desired product (65 mg, 77% yield). MS (apci) m/z=429.2 (M+H).

Workup

  1. temperatureAfter cooling
  2. concentrationthe reaction mixture was concentrated
  3. additionthe resulting residue was diluted with EtOAc (20 mL)
  4. washwashed with saturated aqueous NaHCO3 (5 mL), water (2×5 mL) and brine (5 mL)
  5. dry with materialThe organic layer was dried with Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica column chromatography
  9. washeluting with EtOAc/MeOH/NH4OH 10:1:0.1

Sources & evidence

ORD record
ord-d8d2f22ec6fb43778b5cf480f3a71b0d
Source dataset
uspto-grants-2015_01
Patent number
US08933084B2

Reaction notes

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