1,1'-Carbonyldiimidazole → (S)-N-[5-(4-Methylpiperazin-1-yl)-3,4 dihydro-2H-1-benzopyran-3-yl)-4-(morpholinocarbonyl)benzamide

HRID 433914ノート

反応式

HRID 433914 の反応式
[O:1]1[CH2:6][CH2:5][N:4]([C:7]([C:9]2[CH:17]=[CH:16][C:12]([C:13]([OH:15])=O)=[CH:11][CH:10]=2)=[O:8])[CH2:3][CH2:2]1.C(N1C=CN=C1)([N:20]1C=CN=C1)=O.N[C@H]1C[C:35]([N:37]2[CH2:42][CH2:41][N:40](C)[CH2:39][CH2:38]2)=COC1.[O:44]1[C:49]2[CH:50]=[CH:51][CH:52]=[CH:53][C:48]=2[CH:47]=[CH:46][CH2:45]1>CN(C)C=O>[CH3:35][N:37]1[CH2:42][CH2:41][N:40]([C:53]2[C:48]3[CH2:47][C@H:46]([NH:20][C:13](=[O:15])[C:12]4[CH:11]=[CH:10][C:9]([C:7]([N:4]5[CH2:3][CH2:2][O:1][CH2:6][CH2:5]5)=[O:8])=[CH:17][CH:16]=4)[CH2:45][O:44][C:49]=3[CH:50]=[CH:51][CH:52]=2)[CH2:39][CH2:38]1

参加物

5

反応物 3

HCID 682631,1'-Carbonyldiimidazole2 回HCID 47142364-(Morpholine-4-carbonyl)benzoic acidHCID 69212987(S)-3-Amino-5-(4-methylpiperazin-1-yl)-3,4 dihydropyran 2H-1-benzopyran

生成物 1

HCID 69211129(S)-N-[5-(4-Methylpiperazin-1-yl)-3,4 dihydro-2H-1-benzopyran-3-yl)-4-(morpholinocarbonyl)benzamide収率 53%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒2 回

反応条件

温度
75 °C

実験手順

4-(Morpholinocarbonyl)benzoic acid (100 mg, 0.43 mmol; described in: J. Med. Chem. 1994, 37(26), 4538-4554) and 1,1′-carbonyldiimidazole (76 mg, 0.47 mmol) were dissolved in N,N-dimethylformamide (3 mL) and heated to 75° C. for 3.5 h. Additional 1,1′-carbonyldiimidazole (36 mg, 0.22 mol) was added and the solution was stirred for 30 min. (S)-3-Amino-5-(4-methylpiperazin-1-yl)-3,4 dihydropyran-2H-1-benzopyran (100 mg, 0.40 mmol), dissolved in N,N-dimethylformamide (2 mL), was added and the reaction mixture was stirred for 18 h at 50° C. The solvent was evaporated and the residue was partitioned between ethyl acetate (30 mL) and water (5 mL). The organic layer was washed with water (5 mL) and brine (5 mL) and dried (MgSO4). The solvent was evaporated in vacuo giving 180 mg of a crude product. Purification by preparative TLC twice using chloroform/methanol/concentrated ammonia 95:5:0.5 and chloroform/ethanol (saturated with NH3) 12:1 as the eluents afforded 98 mg (53% yield) of the title compound as a white solid: mp 222° C. (decomposes); EIMS (70 eV) m/z (relative intensity) 464 (68, M+); [α]22D−1220 (c 0.44, chloroform).

後処理

  1. additionwas added
  2. customThe solvent was evaporated
  3. customthe residue was partitioned between ethyl acetate (30 mL) and water (5 mL)
  4. washThe organic layer was washed with water (5 mL) and brine (5 mL)
  5. dry with materialdried (MgSO4)
  6. customThe solvent was evaporated in vacuo
  7. customgiving 180 mg of a crude product
  8. customPurification by preparative TLC twice using chloroform/methanol/concentrated ammonia 95:5:0.5 and chloroform/ethanol (saturated with NH3) 12:1 as the eluents

出典と根拠

ORDレコード
ord-d6bb294808534cc29746bb60b68f7bce
出典データセット
uspto-grants-2003_12
特許番号
US06670359B2

反応ノート

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