Triethylamine → (2S,4S)-tert-butyl 4-(2-([1,2,4]triazolo[4,3-a]pyridin-3-yl)quinolin-8-yloxy)-2-(methoxy(methyl)carbamoyl)piperidine-1-carboxylate

HRID 876425

반응식

HRID 876425 반응식
[N:1]1[N:2]=[C:3]([C:10]2[CH:19]=[CH:18][C:17]3[C:12](=[C:13]([O:20][C@H:21]4[CH2:26][CH2:25][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[C@H:23]([C:34]([OH:36])=O)[CH2:22]4)[CH:14]=[CH:15][CH:16]=3)[N:11]=2)[N:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=12.[CH3:37]CN=C=NCCCN(C)C.C1C=C[C:51]2[N:56]([OH:57])N=NC=2C=1.C(N(CC)CC)C.Cl.CN(C)O>C(Cl)Cl.CCOC(C)=O>[N:1]1[N:2]=[C:3]([C:10]2[CH:19]=[CH:18][C:17]3[C:12](=[C:13]([O:20][C@H:21]4[CH2:26][CH2:25][N:24]([C:27]([O:29][C:30]([CH3:31])([CH3:33])[CH3:32])=[O:28])[C@H:23]([C:34](=[O:36])[N:56]([O:57][CH3:37])[CH3:51])[CH2:22]4)[CH:14]=[CH:15][CH:16]=3)[N:11]=2)[N:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=12

참가 물질

8

반응물 5

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 27969N,N-dimethylhydroxylamine hydrochlorideHCID 757711-HydroxybenzotriazoleHCID 67230757(2S,4S)-4-(2-([1,2,4]triazolo[4,3-a]pyridin-3-yl)quinolin-8-yloxy)-1-(tert-butoxycarbonyl)piperidine-2-carboxylic acid

생성물 1

HCID 86654359(2S,4S)-tert-butyl 4-(2-([1,2,4]triazolo[4,3-a]pyridin-3-yl)quinolin-8-yloxy)-2-(methoxy(methyl)carbamoyl)piperidine-1-carboxylate수율 70%

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 8857Ethyl Acetate용매

반응 조건

온도
0 °C

실험 절차

(2S,4S)-4-(2-([1,2,4]triazolo[4,3-a]pyridin-3-yl)quinolin-8-yloxy)-1-(tert-butoxycarbonyl)piperidine-2-carboxylic acid (Example 53; 0.100 g, 0.204 mmol), EDCI (0.0548 g, 0.286 mmol) and HOBT (0.0359 g, 0.266 mmol) were mixed in CH2Cl2 (2.5 mL) and the mixture was cooled to 0° C. Triethylamine (0.0712 mL, 0.511 mmol) was added and the mixture was stirred for 15 minutes. Dimethyl hydroxylamine HCl (0.0299 g, 0.306 mmol) was added, and the mixture was warmed to ambient temperature and stirred for 4.5 hours. The mixture was diluted with EtOAc (20 mL) and washed with 1N KHSO4 (2×10 mL), followed by a saturated aqueous NaHCO3 solution and brine. The organic layer was dried over Na2SO4, filtered and concentrated. The crude material was purified by column chromatography (1 to 5% MeOH/CH2Cl2) to provide 0.076 g (70%) of the product as a white foam.

후처리

  1. temperaturethe mixture was warmed to ambient temperature
  2. stirringstirred for 4.5 hours
  3. washwashed with 1N KHSO4 (2×10 mL)
  4. dry with materialThe organic layer was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude material was purified by column chromatography (1 to 5% MeOH/CH2Cl2)

출처 및 근거

ORD 기록
ord-039a86732c0e43939758145037c56337
출처 데이터셋
uspto-grants-2015_03
특허 번호
US08987251B2

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