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

HRID 1017615노트

반응식

HRID 1017615 반응식
[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

참가 물질

5

반응물 3

HCID 682631,1'-Carbonyldiimidazole2회HCID 47142364-(Morpholine-4-carbonyl)benzoic acidHCID 69212987(S)-3-Amino-5-(4-methylpiperazin-1-yl)-3,4 dihydropyran 2H-1-benzopyran

생성물 1

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

시약·촉매·용매 1

HCID 6228Dimethylformamide용매2회

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온도
75 °C

실험 절차

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, M30 ); [α]22D−12° (c 0.44, chloroform).

후처리

  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

출처 및 근거

ORD 기록
ord-58eb493013774fdfbf214494076492ac
출처 데이터셋
uspto-grants-2002_11
특허 번호
US06479497B1

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