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

HRID 633740Notes

Reaction equation

HRID 633740 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][CH2:32][CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1>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][CH2:32][CH2:33][C:34]4[CH:39]=[CH:38][CH: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

5

Reactant 3

HCID 10796Cesium carbonateHCID 12503(3-Bromopropyl)benzeneHCID 136950337(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

Product 1

HCID 118194328(8S)-2-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-9-(3-phenylpropyl)-8-trifluoromethyl-6,7,8,9-tetrahydropyrimido[1,2-a]pyrimidin-4-oneYield 36.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

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 790 mg (2.42 mmol) of cesium carbonate in 10 mL of DMF is heated at 90° C. for 10 minutes. After addition of 600 μl (1.21 mmol) of (3-bromopropyl)benzene, the reaction is continued for 2 hours at 90° C. The solvent is evaporated off. The residue is purified by RP18 reverse-phase chromatography (eluent: H2O 100% to CH3CN 100%) to give 100 mg of (8S)-2-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-9-(3-phenylpropyl)-8-trifluoromethyl-6,7,8,9-tetrahydropyrimido[1,2-a]pyrimidin-4-one, the characteristics of which are as follows:

Workup

  1. customThe solvent is evaporated off
  2. customThe residue is purified by RP18 reverse-phase chromatography (eluent: H2O 100% to CH3CN 100%)

Sources & evidence

ORD record
ord-e9c5c19f1dd943559622df5741b0e884
Source dataset
uspto-grants-2016_04
Patent number
US09321790B2

Reaction notes

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