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Acryloyl chloride → N-{3-[(5-cyano-2-[(1-methyl-1H-pyrazol-4-yl)amino]-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)oxy]cyclobutyl}prop-2-enamide

HRID 577679
ノート
印刷プレビュー

反応式

HRID 577679 の反応式
[NH2:1][CH:2]1[CH2:5][CH:4]([O:6][C:7]2[C:8]3[C:22]([C:23]#[N:24])=[CH:21][N:20]([CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:32])([CH3:31])[CH3:30])[C:9]=3[N:10]=[C:11]([NH:13][C:14]3[CH:15]=[N:16][N:17]([CH3:19])[CH:18]=3)[N:12]=2)[CH2:3]1.[C:33](Cl)(=[O:36])[CH:34]=[CH2:35].CCN(C(C)C)C(C)C>C(Cl)Cl>[C:23]([C:22]1[C:8]2[C:7]([O:6][CH:4]3[CH2:3][CH:2]([NH:1][C:33](=[O:36])[CH:34]=[CH2:35])[CH2:5]3)=[N:12][C:11]([NH:13][C:14]3[CH:15]=[N:16][N:17]([CH3:19])[CH:18]=3)=[N:10][C:9]=2[N:20]([CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:32])([CH3:31])[CH3:30])[CH:21]=1)#[N:24]
参加物実験手順後処理出典と根拠反応ノート

参加物

5

反応物 3

HCID 13140Acryloyl chlorideHCID 81531DiisopropylethylamineHCID 866796244-[(3-aminocyclobutyl)oxy]-2-[(1-methyl-1H-pyrazol-4-yl)amino]-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile

生成物 1

HCID 86679625N-{3-[(5-cyano-2-[(1-methyl-1H-pyrazol-4-yl)amino]-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)oxy]cyclobutyl}prop-2-enamide収率 75%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a solution of 4-[(3-aminocyclobutyl)oxy]-2-[(1-methyl-1H-pyrazol-4-yl)amino]-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile (cis:trans 1:1) (380 mg, 0.84 mmol) in DCM (10 mL) was added acryloyl chloride (68 μL, 0.84 mmol) and DIPEA (146 μL, 0.84 mmol). The reaction solution was stirred at rt for 10 min. The reaction mixture was partitioned between DCM (50 mL) and saturated aqueous NaHCO3 (20 mL). The organic layer was separated, dried over Na2SO4 and evaporated. The product was purified via flash chromatography eluting with a gradient of 0%-100% EtOAc in heptanes to give the title compound (317 mg, 75% yield) as a 1:1 cis:trans isomeric mixture. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.43 (s, 1H) 8.42-8.63 (m, 1H) 8.11 (s, 1H) 7.96 (br. s., 1H) 7.43-7.62 (m, 1H) 6.00-6.31 (m, 2H) 5.61 (ddd, J=9.69, 7.05, 2.64 Hz, 3H) 4.07-5.26 (m, 2H) 3.81 (d, J=5.79 Hz, 3H) 3.56 (t, J=7.93 Hz, 2H) 2.84-2.99 (m, 1H) 2.51-2.58 (m, 2H) 2.08-2.20 (m, 1H) 0.84 (t, J=8.06 Hz, 2H) −0.12 (br. s., 9H). m/z (APCI+) for C24H32N8O3Si 509.1 (M+H)+.

後処理

  1. customThe reaction mixture was partitioned between DCM (50 mL) and saturated aqueous NaHCO3 (20 mL)
  2. customThe organic layer was separated
  3. dry with materialdried over Na2SO4
  4. customevaporated
  5. customThe product was purified via flash chromatography
  6. washeluting with a gradient of 0%-100% EtOAc in heptanes

出典と根拠

ORDレコード
ord-6f4309b64db74586a4e8bcff77d2895d
出典データセット
uspto-grants-2015_05
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09040547B2

反応ノート

読み込み中…

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