Diisopropylethylamine → (R)-tert-butyl (1-(5-bromo-3-isobutyramido-1H-pyrrolo[2,3-b]pyridin-4-yl)pyrrolidin-3-yl)methylcarbamate

HRID 1923937ノート

反応式

HRID 1923937 の反応式
[NH:1]1[CH2:5][CH2:4][C@H:3]([CH2:6][NH:7][C:8](=[O:14])[O:9][C:10]([CH3:13])([CH3:12])[CH3:11])[CH2:2]1.[Br:15][C:16]1[C:17](F)=[C:18]2[C:24]([NH:25][C:26](=[O:30])[CH:27]([CH3:29])[CH3:28])=[CH:23][NH:22][C:19]2=[N:20][CH:21]=1.C(N(CC)C(C)C)(C)C.CC#N.O>CCCCO.O>[Br:15][C:16]1[C:17]([N:1]2[CH2:5][CH2:4][C@H:3]([CH2:6][NH:7][C:8](=[O:14])[O:9][C:10]([CH3:11])([CH3:13])[CH3:12])[CH2:2]2)=[C:18]2[C:24]([NH:25][C:26](=[O:30])[CH:27]([CH3:28])[CH3:29])=[CH:23][NH:22][C:19]2=[N:20][CH:21]=1

参加物

7

反応物 4

HCID 81531DiisopropylethylamineHCID 1519426(S)-3-N-Boc-aminomethyl pyrrolidineHCID 18373917Acetonitrile--water (1/1)HCID 60205321N-(5-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)isobutyramide

生成物 1

HCID 86652143(R)-tert-butyl (1-(5-bromo-3-isobutyramido-1H-pyrrolo[2,3-b]pyridin-4-yl)pyrrolidin-3-yl)methylcarbamate収率 61%

試薬・触媒・溶媒 2

HCID 2631-Butanol溶媒HCID 962Water溶媒

反応条件

温度
160 °C

実験手順

(S)-tert-Butyl pyrrolidin-3-ylmethylcarbamate (505 mg, 2.52 mmol) was added to a suspension of N-(5-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)isobutyramide (252 mg, 0.84 mmol) and N,N-diisopropylethylamine (326 mg, 0.439 mL, 2.52 mmol) in n-BuOH (2.5 mL). The resulting mixture was heated in a sealed tube under nitrogen at 160° C. for 18 hours. The cooled mixture was diluted with water and extracted with EtOAc (3×20 mL). The combined organic layer was dried over MgSO4 and filtered, and the filtrate was concentrated to an oil and purified by reverse phase chromatography (Biotage SP4, C-18 25M+, 20-85% CH3CN/water, 25 CV) to give (R)-tert-butyl (1-(5-bromo-3-isobutyramido-1H-pyrrolo[2,3-b]pyridin-4-yl)pyrrolidin-3-yl)methylcarbamate (245 mg, 61% yield) as a solid. LCMS (APCI+) m/z 480.1, 482.1 (M+H)+, Retention time=3.66 minutes.

後処理

  1. extractionextracted with EtOAc (3×20 mL)
  2. dry with materialThe combined organic layer was dried over MgSO4
  3. filtrationfiltered
  4. concentrationthe filtrate was concentrated to an oil
  5. custompurified by reverse phase chromatography (Biotage SP4

出典と根拠

ORDレコード
ord-d1e8708887884b63b991acb3a925e6bf
出典データセット
uspto-grants-2012_05
特許番号
US08178131B2

反応ノート

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