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llms.txt · MCP 가이드개인정보처리방침 · 이용약관 · 지원v1.8.0
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Sodium bis(trimethylsilyl)amide → (5S,6S,9R)-5-azido-6-(2,3-difluorophenyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9-yl 4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxylate

HRID 1879369
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HRID 1879369 반응식
[N:1]([C@@H:4]1[C:14]2[C:9](=[N:10][CH:11]=[CH:12][CH:13]=2)[C@H:8]([OH:15])[CH2:7][CH2:6][C@H:5]1[C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[C:17]=1[F:23])=[N+:2]=[N-:3].[O:24]=[C:25]1[NH:33][C:28]2=[N:29][CH:30]=[CH:31][CH:32]=[C:27]2[N:26]1[CH:34]1[CH2:39][CH2:38][N:37]([C:40](OC2C=CC([N+]([O-])=O)=CC=2)=[O:41])[CH2:36][CH2:35]1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+]>CN(C)C=O>[O:24]=[C:25]1[NH:33][C:28]2=[N:29][CH:30]=[CH:31][CH:32]=[C:27]2[N:26]1[CH:34]1[CH2:35][CH2:36][N:37]([C:40]([O:15][C@H:8]2[C:9]3=[N:10][CH:11]=[CH:12][CH:13]=[C:14]3[C@@H:4]([N:1]=[N+:2]=[N-:3])[C@H:5]([C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[C:17]=3[F:23])[CH2:6][CH2:7]2)=[O:41])[CH2:38][CH2:39]1
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참가 물질

5

반응물 3

HCID 2724254Sodium bis(trimethylsilyl)amideHCID 579114044-nitrophenyl 4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxylateHCID 58467993(5S,6S,9R)-5-azido-6-(2,3-difluorophenyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9-ol

생성물 1

HCID 51357856(5S,6S,9R)-5-azido-6-(2,3-difluorophenyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9-yl 4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxylate
수율 73%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

In a 100 mL round-bottom flask was dissolved (5S,6S,9R)-5-azido-6-(2,3-difluorophenyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9-ol (0.490 g, 1.549 mmol) (azeotroped with dry benzene) and 4-nitrophenyl 4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxylate (0.713 g, 1.859 mmol) in dimethylformamide (8 mL) to give a light yellow suspension under nitrogen. After cooling to −15° C. (ice-methanol bath), NaHMDS (4.18 mL, 4.18 mmol) was added dropwise. The resulting tan solution was stirred under nitrogen at −10° C.˜0° C. for 2 h and at room temperature for 2 h. LCMS showed complete conversion. The reaction was quenched with sodium bicarbonate solution. The mixture was diluted with ethyl acetate. The layers were separated and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with water, brine, dried with sodium sulfate, and concentrated to give a tan oil. Purification by FCC up to 8% methanol/methylene chloride afforded the desired product (major peak, 632 mg, 73% for 3 steps) as a light yellow foam.

후처리

  1. customto give a light yellow suspension under nitrogen
  2. additionwas added dropwise
  3. customThe reaction was quenched with sodium bicarbonate solution
  4. additionThe mixture was diluted with ethyl acetate
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted with ethyl acetate
  7. washThe combined organic layers were washed with water, brine
  8. dry with materialdried with sodium sulfate
  9. concentrationconcentrated
  10. customto give a tan oil
  11. customPurification by FCC up to 8% methanol/methylene chloride

출처 및 근거

ORD 기록
ord-86fbd7efc3fe4ada8575b30c7a64a075
출처 데이터셋
uspto-grants-2012_11
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08314117B2

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