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(3R)-3-Amino-3-[3-[4-(5-ethoxy-2-fluoro-phenyl)-6-methyl-pyrimidin-2-yl]prop-2-ynyl]-1-methyl-pyrrolidin-2-one → (5R)-2-[4-(5-ethoxy-2-fluoro-phenyl)-6-methyl-pyrimidin-2-yl]-7-methyl-1,7-diazaspiro[4.4]non-1-en-6-one

HRID 626901
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인쇄 미리보기

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HRID 626901 반응식
[NH2:1][C@:2]1([CH2:9][C:10]#[C:11][C:12]2[N:17]=[C:16]([C:18]3[CH:23]=[C:22]([O:24][CH2:25][CH3:26])[CH:21]=[CH:20][C:19]=3[F:27])[CH:15]=[C:14]([CH3:28])[N:13]=2)[CH2:6][CH2:5][N:4]([CH3:7])[C:3]1=[O:8]>CC#N.CCOC(C)=O.FC(F)(F)S([O-])(=O)=O.[Ag+]>[CH2:25]([O:24][C:22]1[CH:21]=[CH:20][C:19]([F:27])=[C:18]([C:16]2[CH:15]=[C:14]([CH3:28])[N:13]=[C:12]([C:11]3[CH2:10][CH2:9][C@:2]4([CH2:6][CH2:5][N:4]([CH3:7])[C:3]4=[O:8])[N:1]=3)[N:17]=2)[CH:23]=1)[CH3:26]
참가 물질반응 조건실험 절차후처리출처 및 근거반응 노트

참가 물질

5

반응물 1

HCID 90015517(3R)-3-Amino-3-[3-[4-(5-ethoxy-2-fluoro-phenyl)-6-methyl-pyrimidin-2-yl]prop-2-ynyl]-1-methyl-pyrrolidin-2-one

생성물 1

HCID 90015243(5R)-2-[4-(5-ethoxy-2-fluoro-phenyl)-6-methyl-pyrimidin-2-yl]-7-methyl-1,7-diazaspiro[4.4]non-1-en-6-one수율 74.9%

시약·촉매·용매 3

HCID 76223Silver(I) trifluoromethanesulfonate촉매2회HCID 6342Acetonitrile용매
HCID 8857
Ethyl Acetate
용매

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온도
40 °C

실험 절차

Silver trifluoromethanesulphonate (60.06 mg, 0.23 mmol) was added to a solution of (3R)-3-amino-3-[3-[4-(5-ethoxy-2-fluoro-phenyl)-6-methyl-pyrimidin-2-yl]prop-2-ynyl]-1-methyl-pyrrolidin-2-one (which may be prepared as described in Description 19) (447 mg, 1.17 mmol) in MeCN (20 mL) at 20° C. and the reaction was stirred for 66 hrs. An additional 10 mol % AgOTf was added, stirring was continued for an additional 3 days then the mixture was heated to 40° C. until no starting material remained. The solvent was evaporated and the residue was partitioned between water and EtOAc. The organic layer was dried (Na2SO4) and the solvent was evaporated to afford a brown oil. This was purified using a Biotage Isolera with a 25 g SNAP cartridge, eluting with a 0 to 50% mixture (9% MeOH; 89% EtOAc and 2% 880 NH3) in EtOAc affording the (5R)-2-[4-(5-ethoxy-2-fluoro-phenyl)-6-methyl-pyrimidin-2-yl]-7-methyl-1,7-diazaspiro[4.4]non-1-en-6-one (D20) (335 mg, 0.876 mmol, 74.9% yield) as a light brown solid.

후처리

  1. stirringstirring
  2. waitwas continued for an additional 3 days
  3. customThe solvent was evaporated
  4. customthe residue was partitioned between water and EtOAc
  5. dry with materialThe organic layer was dried (Na2SO4)
  6. customthe solvent was evaporated
  7. customto afford a brown oil
  8. customThis was purified

출처 및 근거

ORD 기록
ord-0535d3f5adc94c0ba6deac88f607b6aa
출처 데이터셋
uspto-grants-2016_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09309254B2

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