Acetic Acid → (R)-ethyl 5-(2-(5-fluoro-2-oxo-1,2-dihydropyridin-3-yl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylate

HRID 1631309Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]([C@H:10]2[CH2:14][CH2:13][CH2:12][N:11]2[C:15]2[CH:20]=[CH:19][N:18]3[N:21]=[CH:22][C:23]([C:24]([O:26][CH2:27][CH3:28])=[O:25])=[C:17]3[N:16]=2)[C:5]([O:8]C)=[N:6][CH:7]=1.CC(O)=O.Br>CCOC(C)=O>[F:1][C:2]1[CH:3]=[C:4]([C@H:10]2[CH2:14][CH2:13][CH2:12][N:11]2[C:15]2[CH:20]=[CH:19][N:18]3[N:21]=[CH:22][C:23]([C:24]([O:26][CH2:27][CH3:28])=[O:25])=[C:17]3[N:16]=2)[C:5](=[O:8])[NH:6][CH:7]=1

Participants

Conditions

Temperature: 90 °C

Procedure

To a mixture of (R)-ethyl 5-(2-(5-fluoro-2-methoxypyridin-3-yl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylate (1.0 g, 2.60 mmol, Preparation K, Step A) and AcOH (7.44 mL, 130 mmol) was added HBr (4.76 mL, 33 wt % in acetic acid, 26 mmol) at ambient temperature. The reaction mixture was heated at 90° C. for 2 hours. After cooling, the reaction mixture was diluted with EtOAc, washed with water, saturated NaHCO3, and brine, dried with MgSO4, filtered and concentrated. The crude material was purified by silica column chromatography, eluting with 2-3% MeOH/DCM to yield the title product (0.73 g, 76%). MS (apci) m/z=372.0 (M+H).

Workup

temperatureAfter cooling
washwashed with water, saturated NaHCO3, and brine
dry with materialdried with MgSO4
filtrationfiltered
concentrationconcentrated
customThe crude material was purified by silica column chromatography
washeluting with 2-3% MeOH/DCM

Sources & evidence

ORD record: ord-38d026e24cbb4aa78ccf6443eef25abe
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08791123B2

Reaction notes

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