Sodium hydride → (8S)-9-((S)-2-hydroxy-2-phenylethyl)-2-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-8-trifluoromethyl-6,7,8,9-tetrahydropyrimido[1,2-a]pyrimidin-4-one

HRID 633742Notes

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.[H-].[Na+].Cl[CH2:27][C@H:28]([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[OH:29]>CN(C=O)C>[OH:29][C@@H:28]([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[CH2:27][N:19]1[C:11]2=[N:10][C:9]([N:3]3[CH2:4][CH:5]4[O:8][CH:1]([CH2:7][CH2:6]4)[CH2:2]3)=[CH:14][C:13](=[O:15])[N:12]2[CH2:16][CH2:17][C@H:18]1[C:20]([F:22])([F:21])[F:23]

Participants

Conditions

Temperature: 50 °C

Procedure

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 in 5 mL of DMF are added to a suspension of 60 mg (1.51 mmol) of sodium hydride in 5 mL of DMF. The reaction mixture is heated at 50° C. for 10 minutes. After addition of 142 mg (0.91 mmol) of (S)-2-chloro-1-phenylethanol, the reaction is continued at 90° C. overnight. The reaction medium is evaporated to dryness. 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 33 mg of (8S)-9-((S)-2-hydroxy-2-phenylethyl)-2-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-8-trifluoromethyl-6,7,8,9-tetrahydropyrimido[1,2-a]pyrimidin-4-one, the characteristics of which are as follows:

Workup

customThe reaction medium is evaporated to dryness
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-1fe535b401f043b9bd0896251707f322
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09321790B2

Reaction notes

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