Sodium hydride → (R)-tert-butyl 3-(6-bromo-9-((2-(trimethylsilyl)ethoxy)methyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrol-4-yloxy)piperidine-1-carboxylate

HRID 60318노트

반응식

HRID 60318 반응식
[OH:1][C@@H:2]1[CH2:7][CH2:6][CH2:5][N:4]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:3]1.[H-].[Na+].[Br:17][C:18]1[N:26]=[CH:25][C:24]2[N:23]([CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:34])([CH3:33])[CH3:32])[C:22]3[N:35]=[CH:36][CH:37]=[C:38](Cl)[C:21]=3[C:20]=2[CH:19]=1.BrC1N=CC2N(COCC[Si](C)(C)C)C3N=C(Cl)C=CC=3C=2C=1>O1CCCC1.O.C(OCC)(=O)C>[Br:17][C:18]1[N:26]=[CH:25][C:24]2[N:23]([CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:33])([CH3:34])[CH3:32])[C:22]3[N:35]=[CH:36][CH:37]=[C:38]([O:1][C@@H:2]4[CH2:7][CH2:6][CH2:5][N:4]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:3]4)[C:21]=3[C:20]=2[CH:19]=1

참가 물질

8

반응물 4

HCID 24758Sodium hydrideHCID 1514398(R)-1-Boc-3-hydroxypiperidineHCID 583650426-Bromo-4-chloro-9-(2-trimethylsilanyl-ethoxymethyl)-9H-dipyrido[2,3-b;4',3'-d]pyrroleHCID 866560476-bromo-2-chloro-9-(2-trimethylsilanyl-ethoxymethyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrole

생성물 1

HCID 58365164(R)-tert-butyl 3-(6-bromo-9-((2-(trimethylsilyl)ethoxy)methyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrol-4-yloxy)piperidine-1-carboxylate

시약·촉매·용매 3

HCID 962Water용매HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

반응 조건

온도
40 °C

실험 절차

To a solution of (R)-tert-butyl 3-hydroxypiperidine-1-carboxylate (64 mg, 0.32 mmol) in tetrahydrofuran (1.2 mL) was added sodium hydride as 60% dispersion in mineral oil (13 mg, 0.32 mmol). The reaction mixture was stirred at ambient temperature for 5 minutes before a mixture of 6-bromo-4-chloro-9-(2-trimethylsilanyl-ethoxymethyl)-9H-dipyrido[2,3-b;4′,3′-d]pyrrole with 6-bromo-2-chloro-9-(2-trimethylsilanyl-ethoxymethyl)-9H-dipyrido[2,3-b;4′,3′-d]pyrrole (4:1, 60 mg, 0.1 mmol) was added in one portion, and the reaction mixture was stirred at this temperature for 10 minutes before being warmed to 40° C. for 2 hours. The cooled reaction mixture was then diluted with water (20 mL) and ethyl acetate (50 mL). The organic layer was separated, dried over sodium sulfate, filtered, concentrated in vacuo, and purified flash chromatography (silica, 4 g, ISCO, 0-65% ethyl acetate in heptane) to afford the title compound as a colorless oil, which was used in the next step without any further purification (60 mg, 70%).

후처리

  1. additionwas added in one portion
  2. customThe cooled reaction mixture
  3. customThe organic layer was separated
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. custompurified flash chromatography (silica, 4 g, ISCO, 0-65% ethyl acetate in heptane)

출처 및 근거

ORD 기록
ord-8e346c3f822b45db97aa39421cbe789f
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09440976B2

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