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

HRID 1169390노트

반응식

HRID 1169390 반응식
[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][NH2:47])[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][NH:47][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]

참가 물질

6

반응물 4

HCID 757711-HydroxybenzotriazoleHCID 1514258tert-Butyl 4-(2-aminoethyl)piperidine-1-carboxylateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 105646997-(4-Methylphenyl)-2,3-dihydrobenzooxepine-4-carboxylic acid

생성물 1

HCID 22989973N-[2-[1-(tert-butoxycarbonyl)piperidin-4-yl]ethyl]-7-(4-methylphenyl)-2,3-dihydro-1-benzooxepine-4-carboxamide수율 67%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

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), 2-[1-(tert-butoxycarbonyl)piperidin-4-yl]ethylamine (1256 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 8 hours. The reaction mixture was concentrated, ethyl acetate (120 ml) was added to the residue and the resulting mixture was washed successively with water (30 ml), an aqueous saturated solution of sodium bicarbonate (20 ml×3) and an aqueous saturated solution of sodium chloride (20 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, ethyl acetate/hexane=1/2→1/1). The objective fractions were concentrated under reduced pressure and were mixed with diisopropyl ether to collect an insoluble material by filtration. The insoluble material was washed with diisopropyl ether and was dried under reduced pressure to obtain N-[2-[1-(tert-butoxycarbonyl)piperidin-4-yl]ethyl]-7-(4-methylphenyl)-2,3-dihydro-1-benzooxepine-4-carboxamide (1.64 g, 3.34 mmol, 67%).

후처리

  1. additionwere added at 0° C
  2. concentrationThe reaction mixture was concentrated
  3. additionethyl acetate (120 ml) was added to the residue
  4. washthe resulting mixture was washed successively with water (30 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
  8. additionwere mixed with diisopropyl ether
  9. customto collect an insoluble material
  10. filtrationby filtration
  11. washThe insoluble material was washed with diisopropyl ether
  12. customwas dried under reduced pressure

출처 및 근거

ORD 기록
ord-5fc504aaa2074891bcefdc69be70b4ca
출처 데이터셋
uspto-grants-2003_09
특허 번호
US06627651B1

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