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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
ノート
印刷プレビュー

反応式

HRID 626901 の反応式
[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]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

5

反応物 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

生成物 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-one収率 74.9%

試薬・触媒・溶媒 3

HCID 76223Silver(I) trifluoromethanesulfonate触媒2 回HCID 6342Acetonitrile溶媒
HCID 8857
Ethyl Acetate
溶媒

反応条件

温度
40 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-0535d3f5adc94c0ba6deac88f607b6aa
出典データセット
uspto-grants-2016_04
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09309254B2

反応ノート

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