1,2-Dimethoxyethane → HCID 178488235、化合物

HRID 897563ノート

反応式

HRID 897563 の反応式
I[C:2]1[C:10]2[C:5](=[N:6][CH:7]=[N:8][C:9]=2[NH2:11])[N:4]([C@H:12]2[CH2:17][CH2:16][C@H:15]([N:18]3[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]3)[CH2:14][CH2:13]2)[N:3]=1.[CH3:25][O:26][C:27]1[CH:32]=[C:31](B2OC(C)(C)C(C)(C)O2)[CH:30]=[CH:29][C:28]=1[NH:42][C:43](=[O:49])[O:44][C:45]([CH3:48])([CH3:47])[CH3:46].C(=O)([O-])[O-].[Na+].[Na+].COCCOC>O>[NH2:11][C:9]1[N:8]=[CH:7][N:6]=[C:5]2[N:4]([C@H:12]3[CH2:17][CH2:16][C@H:15]([N:18]4[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]4)[CH2:14][CH2:13]3)[N:3]=[C:2]([C:31]3[CH:30]=[CH:29][C:28]([NH:42][C:43](=[O:49])[O:44][C:45]([CH3:46])([CH3:47])[CH3:48])=[C:27]([O:26][CH3:25])[CH:32]=3)[C:10]=12

参加物

6

反応物 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 177502214-(tert-Butoxycarbonylamino)-3-methoxyphenylboronic acid, pinacol esterHCID 178481015HCID 178481015、化合物

生成物 1

HCID 178488235HCID 178488235、化合物収率 98%

試薬・触媒・溶媒 1

HCID 962Water溶媒

実験手順

trans-3-Iodo-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (4.0 g, 9.06 mmol), tert-butyl N-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]carbamate (3.48 g, 9.97 mmol), palladium tetrakistriphenyphosphine (0.63 g, 0.64 mmol) and sodium carbonate (2.30 g, 21.75 mmol) were mixed with ethylene glycol dimethyl ether (100 mL) and water (50 mL). The reaction mixture was heated at reflux overnight. Organic solvent was removed under reduced pressure and the aqueous layer was extracted with dichloromethane. The combined organic layer was washed with water then brine, dried over MgSO4, filtered and evaporated. The residue was purified by flash column chromatography using dichloromethane/methanol (80:20) as mobile phase to give trans-tert-butyl N-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)carbamate (4.75 g, 98%). 1H NMR (DMSO-d6) δ 1.48 (m, 11H), 2.02 (m, 6H), 2.15 (s, 3H), 2.35 (m, 5H), 2.53 (m, 4H), 3.87 (s, 3H), 4.64 (m, 1H), 7.20 (m, 2H), 7.90 (d, J=8.15, 1H), 8.03 (s, 1H), 8.22 (s, 1H).

後処理

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux overnight
  3. customOrganic solvent was removed under reduced pressure
  4. extractionthe aqueous layer was extracted with dichloromethane
  5. washThe combined organic layer was washed with water
  6. dry with materialbrine, dried over MgSO4
  7. filtrationfiltered
  8. customevaporated
  9. customThe residue was purified by flash column chromatography

出典と根拠

ORDレコード
ord-f62ac429d0ea4c3fb7c0bc42f62ea214
出典データセット
uspto-grants-2005_07
特許番号
US06921763B2

反応ノート

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