홈MCP워크벤치Skills
홈워크벤치알림마이페이지
llms.txt · MCP 가이드개인정보처리방침 · 이용약관 · 지원v1.8.0
  1. 홈
  2. /반응

Sodium bis(trimethylsilyl)amide → (6S,9R)-6-(2,3-difluorophenyl)-6-hydroxy-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 1879375
노트
인쇄 미리보기

반응식

HRID 1879375 반응식
[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C@:9]1([OH:21])[CH2:19][CH2:18][C@@H:17]([OH:20])[C:12]2=[N:13][CH:14]=[CH:15][CH:16]=[C:11]2[CH2:10]1.[O:22]=[C:23]1[NH:31][C:26]2=[N:27][CH:28]=[CH:29][CH:30]=[C:25]2[N:24]1[CH:32]1[CH2:37][CH2:36][N:35]([C:38](OC2C=CC([N+]([O-])=O)=CC=2)=[O:39])[CH2:34][CH2:33]1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+]>CN(C)C=O>[O:22]=[C:23]1[NH:31][C:26]2=[N:27][CH:28]=[CH:29][CH:30]=[C:25]2[N:24]1[CH:32]1[CH2:33][CH2:34][N:35]([C:38]([O:20][C@H:17]2[C:12]3=[N:13][CH:14]=[CH:15][CH:16]=[C:11]3[CH2:10][C@@:9]([C:3]3[CH:4]=[CH:5][CH:6]=[C:7]([F:8])[C:2]=3[F:1])([OH:21])[CH2:19][CH2:18]2)=[O:39])[CH2:36][CH2:37]1
참가 물질실험 절차후처리출처 및 근거반응 노트

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 58467976(6S,9R)-6-(2,3-difluorophenyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridine-6,9-diol

생성물 1

HCID 51357857(6S,9R)-6-(2,3-difluorophenyl)-6-hydroxy-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 100.3%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

In an oven-dried 100 mL round-bottom flask was dissolved (6S,9R)-6-(2,3-difluorophenyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridine-6,9-diol (71 mg, 0.244 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 (121 mg, 0.317 mmol) in dimethylformamide (2 mL) to give a light yellow suspension under nitrogen. NaHMDS (0.926 mL, 0.926 mmol) was added dropwise. The resulting yellow suspension was stirred under nitrogen at room temperature for 3.5 h. LCMS showed complete conversion. The reaction was quenched with saturated sodium bicarbonate and diluted with ethyl acetate. The layers were separated and the aqueous layer was extracted with ethyl acetate (LCMS showed no product left in the aqueous phase). The combined organic layers were washed with water, brine, dried with sodium sulfate, and concentrated to give a yellow oil. Purification by FCC up to 10% methanol/methylene chloride afforded the desired product (131 mg, 100%) as a white powder. LCMS and HPLC showed >99% purity. MS(ESI)[M+H+]=536.26; 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 11.31 (br. s., 1H) 8.35-8.50 (m, 1H) 7.97-8.11 (m, 1H) 7.31-7.60 (m, 3H) 7.02-7.18 (m, 3H) 6.98 (dd, J=7.48, 5.34 Hz, 1H) 6.03 (d, J=10.68 Hz, 1H) 4.60 (br. s., 2H) 4.40 (br. s., 1H) 3.97 (d, J=14.34 Hz, 1H) 2.80-3.20 (m, 4H) 2.67 (t, J=11.75 Hz, 2H) 2.17-2.40 (m, 2H) 2.08 (t, J=12.67 Hz, 2H) 1.89 (d, J=11.29 Hz, 2H); 19F NMR (470 MHz, CHLOROFORM-d) δ ppm −138.72 (d, J=15.15 Hz, 2F).

후처리

  1. customto give a light yellow suspension under nitrogen
  2. customThe reaction was quenched with saturated sodium bicarbonate
  3. additiondiluted with ethyl acetate
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted with ethyl acetate (LCMS
  6. waitleft in the aqueous phase)
  7. washThe combined organic layers were washed with water, brine
  8. dry with materialdried with sodium sulfate
  9. concentrationconcentrated
  10. customto give a yellow oil
  11. customPurification by FCC up to 10% methanol/methylene chloride

출처 및 근거

ORD 기록
ord-dd41a8fe18764c19a97e37c027cf4d34
출처 데이터셋
uspto-grants-2012_11
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08314117B2

반응 노트

불러오는 중…

이 페이지에서참가 물질실험 절차후처리출처 및 근거반응 노트