Cesium carbonate → HCID 70169281, compound

HRID 1426984Notes

Reaction equation

HRID 1426984 reaction equation
Cl[CH2:2][C@@H:3]([OH:31])[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][CH:20]([OH:22])[CH2:19][C@@H:18]3[C:23]3[CH:28]=[C:27]([F:29])[CH:26]=[CH:25][C:24]=3[OH:30])=[N:13][C:12]=12)=[O:7].C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C>[F:29][C:27]1[CH:26]=[CH:25][C:24]2[O:30][CH2:2][C@@H:3]([OH:31])[CH2:4][NH:5][C:6](=[O:7])[C:8]3=[C:12]4[N:13]=[C:14]([CH:15]=[CH:16][N:11]4[N:10]=[CH:9]3)[N:17]3[C@H:18]([CH2:19][C@@H:20]([OH:22])[CH2:21]3)[C:23]=2[CH:28]=1

Participants

4

Reactant 2

HCID 10796Cesium carbonateHCID 67471069N-((S)-3-chloro-2-hydroxypropyl)-5-((R)-2-(5-fluoro-2-hydroxyphenyl)-4-hydroxypyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide

Product 1

HCID 70169281HCID 70169281, compoundYield 16.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of N-((S)-3-chloro-2-hydroxypropyl)-5-((R)-2-(5-fluoro-2-hydroxyphenyl)-4-hydroxypyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide (0.0407 g, 0.0778 mmol) and Cs2CO3 (0.127 g, 0.389 mmol) in DMF (3.6 mL) was heated at 85° C. for 30 minutes. The reaction mixture was cooled to ambient temperature and filtered. The filtrate was concentrated under reduced pressure to give the crude material which was purified by silica column chromatography, eluting with 0-20% MeOH/EtOAc to afford the crude product. The crude material was purified using chiral column chromatography (Chiral Tech OD-H column, 20% EtOH in hexanes). Isolation of the material having a retention time of about 21.8 minutes afforded the title compound (0.0052 g, 16.2% yield). The stereochemistry of the title compound was confirmed by 1H-NMR nOe experiment. LC/MS (ES+APCI) m/z=414.1 (M+H).

Workup

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. filtrationfiltered
  3. concentrationThe filtrate was concentrated under reduced pressure
  4. customto give the crude material which
  5. customwas purified by silica column chromatography
  6. washeluting with 0-20% MeOH/EtOAc
  7. customto afford the crude product
  8. customThe crude material was purified

Sources & evidence

ORD record
ord-33e093160c4c439cbd02921a921bfec5
Source dataset
uspto-grants-2015_01
Patent number
US08933084B2

Reaction notes

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