Sodium hydride → HCID 178504768、化合物

HRID 536275ノート

反応式

HRID 536275 の反応式
[OH:1][C:2]1[C:11]2[N:10]=[C:9]([NH:12][C:13](=[O:20])[C:14]3[CH:19]=[CH:18][CH:17]=[N:16][CH:15]=3)[N:8]3[CH2:21][CH2:22][N:23]=[C:7]3[C:6]=2[CH:5]=[CH:4][C:3]=1[O:24][CH2:25][CH2:26][CH2:27][N:28]1[CH2:33][CH2:32][O:31][CH2:30][CH2:29]1.[H-].[Na+].Cl[CH2:37][C:38]1[CH:43]=[CH:42][C:41]([S:44]([CH3:47])(=[O:46])=[O:45])=[CH:40][CH:39]=1>CN(C=O)C>[CH3:47][S:44]([C:41]1[CH:42]=[CH:43][C:38]([CH2:37][O:1][C:2]2[C:11]3[N:10]=[C:9]([NH:12][C:13](=[O:20])[C:14]4[CH:19]=[CH:18][CH:17]=[N:16][CH:15]=4)[N:8]4[CH2:21][CH2:22][N:23]=[C:7]4[C:6]=3[CH:5]=[CH:4][C:3]=2[O:24][CH2:25][CH2:26][CH2:27][N:28]2[CH2:29][CH2:30][O:31][CH2:32][CH2:33]2)=[CH:39][CH:40]=1)(=[O:45])=[O:46]

参加物

5

反応物 3

HCID 24758Sodium hydrideHCID 1235301-(Chloromethyl)-4-methanesulfonylbenzeneHCID 178522494HCID 178522494、化合物2 回

生成物 1

HCID 178504768HCID 178504768、化合物収率 70.3%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

N-[7-Hydroxy-8-(3-morpholin-4-ylpropoxy)-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl]nicotinamide (Intermediate H, 0.09 g, 0.20 mmol) was suspended in DMF (2.0 mL) and NaH (0.02 g, 0.30 mmol, 60%) were added. After 20 min at rt 1-(chloromethyl)-4-(methylsulfonyl)benzene (0.06 g, 0.30 mmol) was added and the mixture was stirred at it for 16 h. The DMF was evaporated under reduced pressure and the residue triturated with a mixture of −10% MeOH in CH2Cl2 (4 mL). The mixture was vacuum filtered and the solids were washed well with CH2Cl2. The filtrate was concentrated under reduced pressure, and the residue purified via silica gel chromatography (0-6% MeOH/CH2Cl2). The fractions were combined, and the solvent was evaporated under reduced pressure. Drying under high vacuum gave the title compound (0.087 g, 70%): TLC (5% MeOH/CH2Cl2): Rf=0.47; HPLC MS RT=0.55 min, [M+Na]+=641; 1H NMR (DMSO-d6+2 drops TFA-d) δ: 2.21-2.35 (2H, m), 3.05-3.17 (2H, m), 3.22 (3H, s), 3.31 (2H, m), 3.42-3.52 (2H, m), 3.60-3.72 (2H, m), 3.94-4.04 (2H, m), 4.29 (2H, m), 4.39 (2H, t), 4.56 (2H, m), 5.37 (2H, s), 7.52 (1H, d), 7.72 (1H, dd), 7.85 (2H, d), 8.01 (2H, d), 8.10 (1H, d), 8.66 (1H, d), 8.89 (1H, dd), 9.43 (1H, s).

後処理

  1. customThe DMF was evaporated under reduced pressure
  2. customthe residue triturated with a mixture of −10% MeOH in CH2Cl2 (4 mL)
  3. filtrationfiltered
  4. washthe solids were washed well with CH2Cl2
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customthe residue purified via silica gel chromatography (0-6% MeOH/CH2Cl2)
  7. customthe solvent was evaporated under reduced pressure
  8. customDrying under high vacuum

出典と根拠

ORDレコード
ord-7b43efd286dd47259b9b0477b5152355
出典データセット
uspto-grants-2014_10
特許番号
US08859572B2

反応ノート

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