Cesium carbonate → (6R)-9-fluoro-13-oxa-2,11,16,20,21,24-hexazapentacyclo[16.5.2.02,6.07,12.021,25]pentacosa-1(24),7(12),8,10,18(25),19,22-heptaen-17-one

HRID 1426917Notes

Reaction equation

HRID 1426917 reaction equation
Cl[CH2:2][CH2:3][NH:4][C:5]([C:7]1[CH:8]=[N:9][N:10]2[CH:15]=[CH:14][C:13]([N:16]3[CH2:20][CH2:19][CH2:18][C@@H:17]3[C:21]3[C:22](=[O:28])[NH:23][CH:24]=[C:25]([F:27])[CH:26]=3)=[N:12][C:11]=12)=[O:6].C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C>[F:27][C:25]1[CH:26]=[C:21]2[C:22](=[N:23][CH:24]=1)[O:28][CH2:2][CH2:3][NH:4][C:5](=[O:6])[C:7]1=[C:11]3[N:12]=[C:13]([CH:14]=[CH:15][N:10]3[N:9]=[CH:8]1)[N:16]1[C@@H:17]2[CH2:18][CH2:19][CH2:20]1

Participants

4

Reactant 2

HCID 10796Cesium carbonateHCID 67471101(R)-N-(2-chloroethyl)-5-(2-(5-fluoro-2-oxo-1,2-dihydropyridin-3-yl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide

Product 1

HCID 70168943(6R)-9-fluoro-13-oxa-2,11,16,20,21,24-hexazapentacyclo[16.5.2.02,6.07,12.021,25]pentacosa-1(24),7(12),8,10,18(25),19,22-heptaen-17-oneYield 24.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

A suspension of (R)-N-(2-chloroethyl)-5-(2-(5-fluoro-2-oxo-1,2-dihydropyridin-3-yl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide (78 mg, 0.19 mmol) and Cs2CO3 (314 mg, 0.96 mmol) in DMF (5 mL) was heated at 85° C. for 30 minutes. After filtering through a GF/F paper the reaction was diluted with water (40 mL) and NH4Cl (saturated, 5 mL), then extracted with EtOAc (3×40 mL). The combined organic extracts were dried (Na2SO4), filtered, and concentrated. The crude material was purified by reverse phase column chromatography (Biotage SP4 system C-18 12+M column, 0 to 73% acetonitrile/water), to provide the title product as a white solid (17 mg, 24% yield). MS (apci) m/z=369.2 (M+H).

Workup

  1. filtrationAfter filtering through a GF/F paper the reaction
  2. additionwas diluted with water (40 mL) and NH4Cl (saturated, 5 mL)
  3. extractionextracted with EtOAc (3×40 mL)
  4. dry with materialThe combined organic extracts were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude material was purified by reverse phase column chromatography (Biotage SP4 system C-18 12+M column, 0 to 73% acetonitrile/water)

Sources & evidence

ORD record
ord-f1665ad747a042b1a2d032fb48173e0a
Source dataset
uspto-grants-2015_01
Patent number
US08933084B2

Reaction notes

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