Methanol → tert-Butyl (2S)-2-[(1E)-3-{4-[(3-chloro-4-fluorophenyl)amino]-5,8-dihydropyrido[4',3':4,5]thieno[2,3-d]pyrimidin-7(6H)-yl}-3-oxoprop-1-en-1-yl]pyrrolidine-1-carboxylate

HRID 38516노트

반응식

HRID 38516 반응식
C(OP([CH2:9][C:10]([N:12]1[CH2:33][CH2:32][C:15]2[C:16]3[C:21]([NH:22][C:23]4[CH:28]=[CH:27][C:26]([F:29])=[C:25]([Cl:30])[CH:24]=4)=[N:20][CH:19]=[N:18][C:17]=3[S:31][C:14]=2[CH2:13]1)=[O:11])(=O)OCC)C.[H-].[Na+].[CH:36]([C@@H:38]1[CH2:42][CH2:41][CH2:40][N:39]1[C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])=O.CO>C1COCC1>[Cl:30][C:25]1[CH:24]=[C:23]([NH:22][C:21]2[C:16]3[C:15]4[CH2:32][CH2:33][N:12]([C:10](=[O:11])/[CH:9]=[CH:36]/[C@@H:38]5[CH2:42][CH2:41][CH2:40][N:39]5[C:43]([O:45][C:46]([CH3:47])([CH3:49])[CH3:48])=[O:44])[CH2:13][C:14]=4[S:31][C:17]=3[N:18]=[CH:19][N:20]=2)[CH:28]=[CH:27][C:26]=1[F:29]

참가 물질

6

반응물 4

HCID 887MethanolHCID 24758Sodium hydrideHCID 2734674tert-butyl (2S)-2-formylpyrrolidine-1-carboxylateHCID 58116908Diethyl(2-{4-[(3-chloro-4-fluorophenyl)amino]-5,8-dihydropyrido[4',3':4,5]thieno[2,3-d]pyrimidin-7(6H)-yl}-2-oxoethyl)phosphonate

생성물 1

HCID 58116987tert-Butyl (2S)-2-[(1E)-3-{4-[(3-chloro-4-fluorophenyl)amino]-5,8-dihydropyrido[4',3':4,5]thieno[2,3-d]pyrimidin-7(6H)-yl}-3-oxoprop-1-en-1-yl]pyrrolidine-1-carboxylate

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

실험 절차

A solution of diethyl(2-{4-[(3-chloro-4-fluorophenyl)amino]-5,8-dihydropyrido[4′,3′:4,5]thieno[2,3-d]-pyrimidin-7(6H)-yl}-2-oxoethyl)phosphonate from Example 13A (644 mg, 1.26 mmol) in THF (2.5 mL) was cooled to −78° C. Sodium hydride (60% in mineral oil, 50 mg, 1.26 mmol) was added, and the mixture was stirred for 15 min. Subsequently, a solution of tert-butyl (2S)-2-formylpyrrolidine-1-carboxylate (250 mg, 1.26 mmol) in THF (2.5 mL) was added dropwise. The mixture was slowly warmed to rt and stirred overnight. Methanol was added, and the solvent was removed in vacuo. The crude product was purified by preparative HPLC, and the title compound crystallized from PE/MTBE to yield 397 mg (56%).

후처리

  1. stirringstirred overnight
  2. customthe solvent was removed in vacuo
  3. customThe crude product was purified by preparative HPLC
  4. customthe title compound crystallized from PE/MTBE
  5. customto yield 397 mg (56%)

출처 및 근거

ORD 기록
ord-4b573157deaf400ab2f4ec5e8393e808
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08524722B2

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