Dimethyl Sulfide → HCID 24889389、化合物

HRID 1161725ノート

反応式

HRID 1161725 の反応式
[C:1]([C:5]1[O:9][N:8]=[C:7]([NH:10][C:11]([NH:13][C:14]2[CH:19]=[CH:18][C:17]([C:20]3[N:21]=[C:22]4[N:26]([CH:27]=3)[C:25]3[CH:28]=[CH:29][C:30]([CH2:32][CH2:33][C:34]([N:36]5[CH2:41][CH2:40][N:39]([CH2:42][CH3:43])[CH2:38][CH2:37]5)=O)=[CH:31][C:24]=3[S:23]4)=[CH:16][CH:15]=2)=[O:12])[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].S(C)C>C1COCC1>[C:1]([C:5]1[O:9][N:8]=[C:7]([NH:10][C:11]([NH:13][C:14]2[CH:15]=[CH:16][C:17]([C:20]3[N:21]=[C:22]4[N:26]([CH:27]=3)[C:25]3[CH:28]=[CH:29][C:30]([CH2:32][CH2:33][CH2:34][N:36]5[CH2:41][CH2:40][N:39]([CH2:42][CH3:43])[CH2:38][CH2:37]5)=[CH:31][C:24]=3[S:23]4)=[CH:18][CH:19]=2)=[O:12])[CH:6]=1)([CH3:4])([CH3:2])[CH3:3]

参加物

4

反応物 2

HCID 1068Dimethyl SulfideHCID 44598717HCID 44598717、化合物

生成物 1

HCID 24889389HCID 24889389、化合物

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

実験手順

To a suspension of N-(5-tert-butyl-isoxazol-3-yl)-N′-(4-{7-[3-(4-ethyl-piperazin-1-yl)-3-oxo-propyl]imidazo[2,1-b][1,3]benzothiazol-2-yl}phenyl)urea from Example 12A (0.17 g, 0.28 mmol) in THF (10 mL) at room temperature was added 2.0 M solution of BH3/Me2S in THF (1 mL). The mixture was heated to reflux for 4 hours. The reaction was quenched by dropwise addition of 10% HCl solution and stirred at room temperature for 15 min. The mixture was basified with saturated NaHCO3 solution and was extracted with dichloromethane. The combined organic extracts were dried over MgSO4 and concentrated. The crude product was purified by Flash chromatography with silica gel using a 30-100% hexane/ethyl acetate gradient followed by a 0-20% methanol/ethyl acetate gradient. The appropriate fractions were collected, combined, and concentrated to give free base, N-(5-tert-butyl-isoxazol-3-yl)-N′-(4-{7-[3-(4-ethyl-piperazin-1-yl)propyl]imidazo[2,1-b][1,3]benzothiazol-2-yl}phenyl)urea. The free base was dissolved in dichloromethane (about 1 mL) and methanol (a few drops). To this solution was added dropwise a 1.0 M solution of HCl/ether (1.3 equivalents) and a precipitate was formed. After evaporation of the solvents, the residue was taken up in ether, filtered, and washed with ether to give the product as a white solid (0.011 g, 6%). 1H NMR (DMSO-d6) δ 9.6 (s, 1H), 9.07 (s, 1H), 8.69 (s, 1H), 7.92 (m, 2H), 7.78 (d, 2H), 7.54 (d, 2H), 7.48 (d, 1H), 6.53 (s, 1H), 3.50 (4H, overlapping with solvent), 3.22 (m, 6H), 2.75 (m, 4H), 2.10 (m, 2H), 1.30 (s, 9H), 1.24 (t, 3H); LC-MS: ESI 586 (M+H)+.

後処理

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 4 hours
  3. customThe reaction was quenched by dropwise addition of 10% HCl solution
  4. extractionwas extracted with dichloromethane
  5. dry with materialThe combined organic extracts were dried over MgSO4
  6. concentrationconcentrated
  7. customThe crude product was purified by Flash chromatography with silica gel using a 30-100% hexane/ethyl acetate gradient
  8. customThe appropriate fractions were collected
  9. concentrationconcentrated

出典と根拠

ORDレコード
ord-b3dd5792303f45ea8507f464cfe30992
出典データセット
uspto-grants-2010_10
特許番号
US07820657B2

反応ノート

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