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 80625노트

반응식

HRID 80625 반응식
[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

참가 물질

8

반응물 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

생성물 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

시약·촉매·용매 4

HCID 94433Tetrabutylammonium hydrogen sulfate촉매HCID 962Water용매HCID 1140Toluene용매HCID 8857Ethyl Acetate용매

실험 절차

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:

후처리

  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

출처 및 근거

ORD 기록
ord-e697ecd0b908460499ea9bc15fa69867
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08846670B2

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