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 60318ノート

反応式

HRID 60318 の反応式
[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

参加物

8

反応物 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

生成物 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

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
40 °C

実験手順

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%).

後処理

  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)

出典と根拠

ORDレコード
ord-8e346c3f822b45db97aa39421cbe789f
出典データセット
uspto-grants-2016_09
特許番号
US09440976B2

反応ノート

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