1,1'-Carbonyldiimidazole → (S)-N-(3-chloropropyl)-5-(4-(5-fluoro-2-methoxypyridin-3-yl)-2-oxooxazolidin-3-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide

HRID 1426960Notes

Reaction equation

HRID 1426960 reaction equation
[Cl:1][CH2:2][CH2:3][CH2:4][NH:5][C:6]([C:8]1[CH:9]=[N:10][N:11]2[CH:16]=[CH:15][C:14]([NH:17][C@@H:18]([C:21]3[C:22]([O:28][CH3:29])=[N:23][CH:24]=[C:25]([F:27])[CH:26]=3)[CH2:19][OH:20])=[N:13][C:12]=12)=[O:7].C1N=CN([C:35](N2C=NC=C2)=[O:36])C=1>C(#N)C>[Cl:1][CH2:2][CH2:3][CH2:4][NH:5][C:6]([C:8]1[CH:9]=[N:10][N:11]2[CH:16]=[CH:15][C:14]([N:17]3[C@@H:18]([C:21]4[C:22]([O:28][CH3:29])=[N:23][CH:24]=[C:25]([F:27])[CH:26]=4)[CH2:19][O:20][C:35]3=[O:36])=[N:13][C:12]=12)=[O:7]

Participants

4

Reactant 2

HCID 682631,1'-CarbonyldiimidazoleHCID 86691744(S)-N-(3-chloropropyl)-5-(1-(5-fluoro-2-methoxypyridin-3-yl)-2-hydroxyethylamino)pyrazolo[1,5-a]pyrimidine-3-carboxamide

Product 1

HCID 86691745(S)-N-(3-chloropropyl)-5-(4-(5-fluoro-2-methoxypyridin-3-yl)-2-oxooxazolidin-3-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamideYield 58.9%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of (S)-N-(3-chloropropyl)-5-(1-(5-fluoro-2-methoxypyridin-3-yl)-2-hydroxyethylamino)pyrazolo[1,5-a]pyrimidine-3-carboxamide (60 mg, 0.14 mmol) in ACN (2 mL) was added CDI (35 mg, 0.21 mmol). The solution was stirred at ambient temperature for 16 hours then partitioned between saturated NH4Cl solution (20 mL) and EtOAc (10 mL) and the layers separated. The aqueous layer was extracted with EtOAc (2×10 mL) and the combined organic phases were washed with brine (10 mL), dried over Na2SO4, filtered and concentrated. The residue was purified by flash column chromatography eluting with 1% MeOH/DCM to afford (S)-N-(3-chloropropyl)-5-(4-(5-fluoro-2-methoxypyridin-3-yl)-2-oxooxazolidin-3-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide (37 mg, 58% yield) as a white solid. MS (apci) m/z=449.0 (M+H).

Workup

  1. customthen partitioned between saturated NH4Cl solution (20 mL) and EtOAc (10 mL)
  2. customthe layers separated
  3. extractionThe aqueous layer was extracted with EtOAc (2×10 mL)
  4. washthe combined organic phases were washed with brine (10 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by flash column chromatography
  9. washeluting with 1% MeOH/DCM

Sources & evidence

ORD record
ord-522a4497e71e47b189628d343a5195b5
Source dataset
uspto-grants-2015_01
Patent number
US08933084B2

Reaction notes

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