Sodium Hydroxide → (8S)-9-[2-(3-fluorophenyl)ethyl]-2-(morpholin-4-yl)-8-(trifluoromethyl)-6,7,8,9-tetrahydro-4H-pyrimido[1,2-a]pyrimidin-4-one

HRID 80625ノート

反応式

HRID 80625 の反応式
[OH-].[Na+].Br[CH2:4][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([F:12])[CH:7]=1.[N:13]1([C:19]2[N:20]=[C:21]3[NH:29][C@H:28]([C:30]([F:33])([F:32])[F:31])[CH2:27][CH2:26][N:22]3[C:23](=[O:25])[CH:24]=2)[CH2:18][CH2:17][O:16][CH2:15][CH2:14]1>O.S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC.C1(C)C=CC=CC=1.C(OCC)(=O)C>[F:12][C:8]1[CH:7]=[C:6]([CH2:5][CH2:4][N:29]2[C:21]3=[N:20][C:19]([N:13]4[CH2:18][CH2:17][O:16][CH2:15][CH2:14]4)=[CH:24][C:23](=[O:25])[N:22]3[CH2:26][CH2:27][C@H:28]2[C:30]([F:31])([F:32])[F:33])[CH:11]=[CH:10][CH:9]=1

参加物

8

反応物 3

HCID 14798Sodium HydroxideHCID 5731291-(2-Bromoethyl)-3-fluorobenzeneHCID 136238743(S)-8-(Morpholin-4-yl)-2-(trifluoromethyl)-1,2,3,4-tetrahydropyrimido[1,2-a]pyrimidin-6-one

生成物 1

HCID 49854500(8S)-9-[2-(3-fluorophenyl)ethyl]-2-(morpholin-4-yl)-8-(trifluoromethyl)-6,7,8,9-tetrahydro-4H-pyrimido[1,2-a]pyrimidin-4-one

試薬・触媒・溶媒 4

HCID 94433Tetrabutylammonium hydrogen sulfate触媒HCID 962Water溶媒HCID 1140Toluene溶媒HCID 8857Ethyl Acetate溶媒

実験手順

296 mg of sodium hydroxide in 2.5 ml of water, 33 mg of tetrabutylammonium hydrogen sulphate and 200 mg of 1-(2-bromoethyl)-3-fluorobenzene are added to a solution of 150 mg of (8S)-2-(morpholin-4-yl)-8-(trifluoromethyl)-6,7,8,9-tetrahydro-4 H-pyrimido[1,2-a]pyrimidin-4-one in 2.5 ml of toluene. After one hour under microwave irradiation (power 100 watts on a CEM discover apparatus) at 60° C. and then one hour again at 60° C. and twice six hours at 70° C., the reaction mixture is diluted with ethyl acetate. The resulting mixture is washed with water. The organic phase is separated and then concentrated to dryness under reduced pressure. After purification of the resulting residue by preparative HPLC/MS (method D), 43 mg of (8S)-9-[2-(3-fluorophenyl)ethyl]-2-(morpholin-4-yl)-8-(trifluoromethyl)-6,7,8,9-tetrahydro-4 H-pyrimido[1,2-a]pyrimidin-4-one are obtained, the characteristics of which are the following:

後処理

  1. customAfter one hour under microwave irradiation (power 100 watts on a CEM
  2. customat 60° C.
  3. washThe resulting mixture is washed with water
  4. customThe organic phase is separated
  5. concentrationconcentrated to dryness under reduced pressure
  6. customAfter purification of the resulting residue by preparative HPLC/MS (method D), 43 mg of (8S)-9-[2-(3-fluorophenyl)ethyl]-2-(morpholin-4-yl)-8-(trifluoromethyl)-6,7,8,9-tetrahydro-4 H-pyrimido[1,2-a]pyrimidin-4-one
  7. customare obtained

出典と根拠

ORDレコード
ord-e697ecd0b908460499ea9bc15fa69867
出典データセット
uspto-grants-2014_09
特許番号
US08846670B2

反応ノート

読み込み中…