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

HRID 1426927Notes

Reaction equation

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

Participants

Conditions

Temperature: 90 °C

Procedure

A mixture of (R)-2-chloroethyl 5-(2-(5-fluoro-2-oxo-1,2-dihydropyridin-3-yl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylate (54 mg, 0.133 mmol) and Cs2CO3 (217 mg, 0.665 mmol) in DMF (6 mL) was heated at 90° C. overnight. The reaction was filtered (GF/F paper) and directly purified by reverse phase column chromatography (Biotage SP4 system C18 25+M, 5 to 60% acetonitrile/water) to yield a mixture of desired product and impurities. This mixture was treated with a second column chromatography on Biotage SNAP KP-Sil 10 g, eluting with 10% hexanes/EtOAc to give the pure title product as a white solid (11 mg, 22% yield). MS (apci pos) m/z=370.2 (M+H).

Workup

filtrationThe reaction was filtered (GF/F paper)
customdirectly purified by reverse phase column chromatography (Biotage SP4 system C18 25+M, 5 to 60% acetonitrile/water)
customto yield

Sources & evidence

ORD record: ord-47b82d3a88cf4c6593818dfaa0fa285b
Source dataset: uspto-grants-2015_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08933084B2

Reaction notes

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