1-Hydroxybenzotriazole → N-[3-[1-(tert-butoxycarbonyl)piperidin-4-yl]propyl]-7-(4-methylphenyl)-2,3-dihydro-1-benzooxepine-4-carboxamide

HRID 1169392ノート

反応式

HRID 1169392 の反応式
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[CH:10][C:11]3[O:17][CH2:16][CH2:15][C:14]([C:18](O)=[O:19])=[CH:13][C:12]=3[CH:21]=2)=[CH:4][CH:3]=1.ON1C2C=CC=CC=2N=N1.[C:32]([O:36][C:37]([N:39]1[CH2:44][CH2:43][CH:42]([CH2:45][CH2:46][CH2:47][NH2:48])[CH2:41][CH2:40]1)=[O:38])([CH3:35])([CH3:34])[CH3:33].Cl.CN(C)CCCN=C=NCC>CN(C=O)C>[C:32]([O:36][C:37]([N:39]1[CH2:44][CH2:43][CH:42]([CH2:45][CH2:46][CH2:47][NH:48][C:18]([C:14]2[CH2:15][CH2:16][O:17][C:11]3[CH:10]=[CH:9][C:8]([C:5]4[CH:4]=[CH:3][C:2]([CH3:1])=[CH:7][CH:6]=4)=[CH:21][C:12]=3[CH:13]=2)=[O:19])[CH2:41][CH2:40]1)=[O:38])([CH3:35])([CH3:34])[CH3:33]

参加物

6

反応物 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 105646997-(4-Methylphenyl)-2,3-dihydrobenzooxepine-4-carboxylic acidHCID 22990164tert-Butyl 4-(3-aminopropyl)piperidine-1-carboxylate

生成物 1

HCID 22989950N-[3-[1-(tert-butoxycarbonyl)piperidin-4-yl]propyl]-7-(4-methylphenyl)-2,3-dihydro-1-benzooxepine-4-carboxamide収率 99%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

To 7-(4-methylphenyl)-2,3-dihydro-1-benzooxepine-4-carboxylic acid (1402 mg, 5.00 mmol) dissolved in DMF (30 ml) were added at 0° C. 1-hydroxybenzotriazole (743 mg, 5.50 mmol), 3-[1-(tert-butoxycarbonyl)piperidin-4-yl]propylamine (1333 mg, 5.50 mmol) and 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (1438 mg, 7.50 mmol), and the resulting mixture was stirred at room temperature for 18 hours. The reaction mixture was concentrated under reduced pressure, ethyl acetate (100 ml) was added to the residue and the resulting mixture was washed successively with water (10×3 ml), a 10% aqueous solution of potassium hydrogensulfate (10 ml×3), an aqueous saturated solution of sodium bicarbonate (10 ml×3) and an aqueous saturated solution of sodium chloride (10 ml). The organic layer was dried with anhydrous magnesium sulfate and was then concentrated under reduced pressure, and the residue was subjected to column chromatography (silica gel 80g, ethyl acetate/hexane=1/3→1/1)]. The objective fractions were concentrated under reduced pressure to obtain N-[3-[1-(tert-butoxycarbonyl)piperidin-4-yl]propyl]-7-(4-methylphenyl)-2,3-dihydro-1-benzooxepine-4-carboxamide (2498 mg, 4.95 mmol, 99%).

後処理

  1. additionwere added at 0° C
  2. concentrationThe reaction mixture was concentrated under reduced pressure, ethyl acetate (100 ml)
  3. additionwas added to the residue
  4. washthe resulting mixture was washed successively with water (10×3 ml)
  5. dry with materialThe organic layer was dried with anhydrous magnesium sulfate
  6. concentrationwas then concentrated under reduced pressure
  7. concentrationThe objective fractions were concentrated under reduced pressure

出典と根拠

ORDレコード
ord-2e5eafcb179e475396f629ae3375d2c7
出典データセット
uspto-grants-2003_09
特許番号
US06627651B1

反応ノート

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