1,2-Dichloroethane → Ethyl (+/-)-10,11-dihydro-3-[[[(1H-benzimidazol-2-yl)methyl]methylamino]carbonyl]5H-dibenzo[a,d]cycloheptene-10-acetate

HRID 613382ノート

反応式

HRID 613382 の反応式
[CH2:1](Cl)[CH2:2]Cl.[C:5]([C:8]1C=C[C:11]2[CH2:17][CH:16]([CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20])[C:15]3[CH:24]=[CH:25]C=CC=3C[C:12]=2[CH:28]=1)(O)=[O:6].Cl.Cl.[CH3:31][NH:32][CH2:33][C:34]1[NH:35][C:36]2[CH:42]=[CH:41][CH:40]=[CH:39][C:37]=2[N:38]=1.[CH:43]1[CH:44]=CC2N(O)N=N[C:47]=2[CH:48]=1.O.C(N(C(C)C)CC)(C)C>CN(C=O)C>[NH:38]1[C:37]2[CH:39]=[CH:40][CH:41]=[CH:42][C:36]=2[N:35]=[C:34]1[CH2:33][N:32]([CH3:31])[C:5]([C:8]1[CH:28]=[CH:12][C:11]2[CH2:17][CH:16]([CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20])[C:15]3[CH:24]=[CH:25][CH:44]=[CH:43][C:48]=3[CH2:47][C:1]=2[CH:2]=1)=[O:6]

参加物

8

反応物 6

HCID 111,2-DichloroethaneHCID 962WaterHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 13169407((1H-1,3-benzodiazol-2-yl)methyl)(methyl)amine dihydrochlorideHCID 15516628Ethyl (+/-)-10,11-dihydro-3-carboxy-5H-dibenzo[a,d]cycloheptene-10-acetate

生成物 1

HCID 54459000Ethyl (+/-)-10,11-dihydro-3-[[[(1H-benzimidazol-2-yl)methyl]methylamino]carbonyl]5H-dibenzo[a,d]cycloheptene-10-acetate

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

EDC (202.4 mg, 1.06 mmol) was added all at once to a solution of ethyl (±)-10,11-dihydro-3-carboxy-5H-dibenzo[a,d]cycloheptene-10-acetate (285.6 mg, 0.88 mmol), 2-(methylamino)methylbenzimidazole dihydrochloride (247.2 mg, 1.06 mmol), HOBt.H2O (142.7 mg, 1.06 mmol), and diisopropylethylamine (0.61 mL, 3.52 mmol) in anhydrous DMF (4.4 mL) at RT. The reaction was stirred at RT for 16.5 h, then was concentrated on the rotavap (high vacuum). The residue was reconcentrated from xylenes, then was dissolved in H2O (5 mL). EtOAc extraction (2×5 mL), drying (MgSO4), concentration, and chromatography (silica gel, 5% MeOH in 1:1 EtOAc/CHCl3) gave the title compound as a faintly yellow foam (389.2 mg, 95%): TLC Rf (10% MeOH in 1:1 EtOAc/CHCl3) 0.60; 1H NMR (400 MHz, CDCl3) δ 7.70-7.80 (m, 1H), 7.40-7.50 (m, 1H), 7.35 (s, 1H), 7.21-7.32 (m, 3H), 7.04-7.21 (m, 5H), 4.76-4.88 (m, 2H), 4.36 (d, J=15.2 Hz, 1H), 4.18 (q, J=7.1 Hz, 2H), 3.90 (d, J=15.2 Hz, 1H), 3.82-3.95 (m, 1H), 3.38 (dd, J=15.4, 4.0 Hz, 1H), 3.11 (s, 3H), 3.03 (dd, J=15.4, 9.5 Hz, 1H), 2.69 (dd, J=15.8, 4.8 Hz, 1H), 2.52 (dd, J=15.8, 9.6 Hz, 1H), 1.27 (t, J=7.1 Hz, 3H); FTIR (CCl4) 2700-3470 (broad), 1735, 1629 (shoulder), 1617, 1484, 1454, 1422, 1397, 1271, 1180, 1157 cm-1 ; MS (ES) m/e 468.2 (M+H)+.

後処理

  1. customat RT
  2. concentrationwas concentrated on the rotavap (high vacuum)
  3. dissolutionwas dissolved in H2O (5 mL)
  4. extractionEtOAc extraction (2×5 mL)
  5. customdrying
  6. concentration(MgSO4), concentration, and chromatography (silica gel, 5% MeOH in 1:1 EtOAc/CHCl3)

出典と根拠

ORDレコード
ord-b9d1d29a4e024eb584bf6dbba0c21b2a
出典データセット
uspto-grants-1999_12
特許番号
US06008213

反応ノート

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