Cesium carbonate → (8S)-2-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-9-(2-oxo-2-pyrid-4-ylethyl)-8-trifluoromethyl-6,7,8,9-tetrahydropyrimido[1,2-a]pyrimidin-4-one

HRID 633741Notes

Reaction equation

[CH:1]12[O:8][CH:5]([CH2:6][CH2:7]1)[CH2:4][N:3]([C:9]1[N:10]=[C:11]3[NH:19][C@H:18]([C:20]([F:23])([F:22])[F:21])[CH2:17][CH2:16][N:12]3[C:13](=[O:15])[CH:14]=1)[CH2:2]2.C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:31][C:32]([C:34]1[CH:39]=[CH:38][N:37]=[CH:36][CH:35]=1)=[O:33]>CN(C=O)C>[CH:1]12[O:8][CH:5]([CH2:6][CH2:7]1)[CH2:4][N:3]([C:9]1[N:10]=[C:11]3[N:19]([CH2:31][C:32](=[O:33])[C:34]4[CH:39]=[CH:38][N:37]=[CH:36][CH:35]=4)[C@H:18]([C:20]([F:22])([F:21])[F:23])[CH2:17][CH2:16][N:12]3[C:13](=[O:15])[CH:14]=1)[CH2:2]2

Participants

Conditions

Temperature: 0 °C

Procedure

A solution of 200 mg (0.61 mmol) of (8S)-2-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-8-trifluoromethyl-6,7,8,9-tetrahydropyrimido[1,2-a]pyrimidin-4-one and 1.18 g (3.63 mmol) of cesium carbonate in 10 mL of DMF is heated at 90° C. for 10 minutes. The mixture is cooled to 0° C. and 340 mg (1.21 mmol) of 2-bromo-1-pyrid-4-ylethanone are then added. The reaction is continued for 2 hours at room temperature. The solvent is evaporated off. The residue is purified by chromatography on a column of silica (eluent: 90/10 DCM/MeOH). The isolated fraction is recrystallized from acetonitrile to give 16 mg of (8S)-2-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-9-(2-oxo-2-pyrid-4-ylethyl)-8-trifluoromethyl-6,7,8,9-tetrahydropyrimido[1,2-a]pyrimidin-4-one, the characteristics of which are as follows:

Workup

customThe solvent is evaporated off
customThe residue is purified by chromatography on a column of silica (eluent: 90/10 DCM/MeOH)
customThe isolated fraction is recrystallized from acetonitrile

Sources & evidence

ORD record: ord-f1af1507a4bc4caf8fe78aaf4e8c8360
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09321790B2

Reaction notes

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