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(3S)-3-amino-1-methyl-3-[3-[4-methyl-6-[4-(trifluoromethyl)phenyl]-pyrimidin-2-yl]prop-2-ynyl]pyrrolidin-2-one → (55)-7-Methyl-2-[4-methyl-6-[4-(trifluoromethyl)phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]non-1-en-6-one

HRID 2207697
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인쇄 미리보기

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HRID 2207697 반응식
[NH2:1][C@@:2]1([CH2:9][C:10]#[C:11][C:12]2[N:17]=[C:16]([CH3:18])[CH:15]=[C:14]([C:19]3[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][CH:20]=3)[N:13]=2)[CH2:6][CH2:5][N:4]([CH3:7])[C:3]1=[O:8]>CC#N.FC(F)(F)S([O-])(=O)=O.[Ag+]>[CH3:7][N:4]1[CH2:5][CH2:6][C@:2]2([N:1]=[C:11]([C:12]3[N:17]=[C:16]([CH3:18])[CH:15]=[C:14]([C:19]4[CH:20]=[CH:21][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:23][CH:24]=4)[N:13]=3)[CH2:10][CH2:9]2)[C:3]1=[O:8]
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

4

반응물 1

HCID 90014870(3S)-3-amino-1-methyl-3-[3-[4-methyl-6-[4-(trifluoromethyl)phenyl]-pyrimidin-2-yl]prop-2-ynyl]pyrrolidin-2-one

생성물 1

HCID 90014725(55)-7-Methyl-2-[4-methyl-6-[4-(trifluoromethyl)phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]non-1-en-6-one수율 92.6%

시약·촉매·용매 2

HCID 76223Silver(I) trifluoromethanesulfonate촉매2회HCID 6342Acetonitrile용매

실험 절차

Silver trifluoromethanesulphonate (358.56 mg, 1.4 mmol) was added to a solution of (3S)-3-amino-1-methyl-3-[3-[4-methyl-6-[4-(trifluoromethyl)phenyl]pyrimidin-2-yl]prop-2-ynyl]pyrrolidin-2-one (2.71 g, 6.98 mmol) (which may be prepared as described in Description 8) in MeCN (60 mL) at 50° C. and the reaction was stirred for 3 days. Additional AgOTf (10 mol %) was added and stirring was continued for 24 hrs. The solvent was evaporated and the residue was suspended in EtOAc. The organics were washed with water, dried (Na2SO4) and the solvent evaporated to afford a light brown oil. This was purified using a Biotage Isolera with a 100 g SNAP cartridge, eluting with 0 to 100% (mixture of 1% of 2M NH3 in MeOH; 9% MeOH; 90% EtOAc) in EtOAc, affording the (55)-7-methyl-2-[4-methyl-6-[4-(trifluoromethyl)phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]non-1-en-6-one (D9) (2.51 g, 6.4626 mmol, 92.6% yield) as a light brown solid;

후처리

  1. stirringstirring
  2. waitwas continued for 24 hrs
  3. customThe solvent was evaporated
  4. washThe organics were washed with water
  5. dry with materialdried (Na2SO4)
  6. customthe solvent evaporated
  7. customto afford a light brown oil
  8. customThis was purified
  9. washeluting with 0 to 100% (mixture of 1% of 2M NH3 in MeOH; 9% MeOH; 90% EtOAc) in EtOAc

출처 및 근거

ORD 기록
ord-5ff6479ef0e5444a99cd085d92581a1d
출처 데이터셋
uspto-grants-2016_06
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09376445B2

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