Cesium carbonate → (6R)-9-fluoro-13-oxa-2,11,17,21,22,25-hexazapentacyclo[17.5.2.02,6.07,12.022,26]hexacosa-1(25),7(12),8,10,19(26),20,23-heptaen-18-one

HRID 1426910Notes

Reaction equation

HRID 1426910 reaction equation
Cl[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[CH2:21][CH2:20][CH2:19][C@@H:18]3[C:22]3[C:23]([OH:29])=[N:24][CH:25]=[C:26]([F:28])[CH:27]=3)=[N:13][C:12]=12)=[O:7].C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C>[F:28][C:26]1[CH:27]=[C:22]2[C:23](=[N:24][CH:25]=1)[O:29][CH2:2][CH2:3][CH2:4][NH:5][C:6](=[O:7])[C:8]1=[C:12]3[N:13]=[C:14]([CH:15]=[CH:16][N:11]3[N:10]=[CH:9]1)[N:17]1[C@@H:18]2[CH2:19][CH2:20][CH2:21]1

Participants

4

Reactant 2

HCID 10796Cesium carbonateHCID 178523335HCID 178523335, compound

Product 1

HCID 86691719(6R)-9-fluoro-13-oxa-2,11,17,21,22,25-hexazapentacyclo[17.5.2.02,6.07,12.022,26]hexacosa-1(25),7(12),8,10,19(26),20,23-heptaen-18-oneYield 44%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

A DMF (1 mL) suspension of (R)-N-(3-chloropropyl)-5-(2-(5-fluoro-2-hydroxypyridin-3-yl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide (5 mg, 0.012 mmol) and Cs2CO3 (4 mg, 0.06 mmol) was heated at 85° C. overnight. The reaction mixture was filtered through a GF/F paper and directly purified on reverse phase column chromatography (Biotage SP4 system C-18 12+M column, 5 to 60% acetonitrile/water), to provide the title product as white solid (2 mg, 44% yield). MS (apci) m/z=383.3 (M+H).

Workup

  1. filtrationThe reaction mixture was filtered through a GF/F paper
  2. customdirectly purified on reverse phase column chromatography (Biotage SP4 system C-18 12+M column, 5 to 60% acetonitrile/water)

Sources & evidence

ORD record
ord-479168c0841b4d1382566433b2eec8ac
Source dataset
uspto-grants-2015_01
Patent number
US08933084B2

Reaction notes

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