N-Methylethylamine → N-ethyl-6-(4-{1-[8-(hydroxymethyl)-8-methyl-5,6,8,9-tetrahydro[1,2,4]triazolo[4,3-d][1,4]thiazepin-3-yl]cyclopropyl}phenyl)-N-methyl nicotinamide

HRID 1424119노트

반응식

HRID 1424119 반응식
[OH:1][CH2:2][C:3]1([CH3:31])[S:9][CH2:8][CH2:7][N:6]2[C:10]([C:13]3([C:16]4[CH:21]=[CH:20][C:19]([C:22]5[CH:30]=[CH:29][C:25]([C:26]([OH:28])=O)=[CH:24][N:23]=5)=[CH:18][CH:17]=4)[CH2:15][CH2:14]3)=[N:11][N:12]=[C:5]2[CH2:4]1.[CH2:32]([NH:34][CH3:35])[CH3:33].Cl.C(N=C=NCCCN(C)C)C.C(=O)([O-])O.[Na+]>CN(C)C=O>[CH2:32]([N:34]([CH3:35])[C:26](=[O:28])[C:25]1[CH:29]=[CH:30][C:22]([C:19]2[CH:18]=[CH:17][C:16]([C:13]3([C:10]4[N:6]5[CH2:7][CH2:8][S:9][C:3]([CH2:2][OH:1])([CH3:31])[CH2:4][C:5]5=[N:12][N:11]=4)[CH2:14][CH2:15]3)=[CH:21][CH:20]=2)=[N:23][CH:24]=1)[CH3:33]

참가 물질

6

반응물 4

HCID 12219N-MethylethylamineHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 867129516-(4-{1-[8-(Hydroxymethyl)-8-methyl-5,6,8,9-tetrahydro[1,2,4]triazolo[4,3-d][1,4]thiazepin-3-yl]cyclopropyl}phenyl)nicotinic acid

생성물 1

HCID 86712966N-ethyl-6-(4-{1-[8-(hydroxymethyl)-8-methyl-5,6,8,9-tetrahydro[1,2,4]triazolo[4,3-d][1,4]thiazepin-3-yl]cyclopropyl}phenyl)-N-methyl nicotinamide수율 8.2%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

A solution of the compound (200 mg, 0.458 mmol) obtained in Example 66, ethylmethylamine (197 μL, 2.29 mmol), N,N-dimethylaminopyridine (6 mg, 46 mmol), and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (264 mg, 1.37 mmol) in N,N-dimethylformamide (4.00 mL) was stirred at room temperature for 14 h. Saturated aqueous sodium hydrogencarbonate (100 mL) was added to the reaction mixture, the mixture was extracted with dichloromethane, and the organic layer was washed with water and dried with anhydrous sodium sulfate. Then the solvent was distilled off under reduced pressure. The residue was purified by preparative TLC (dichloromethane:methanol=9:1) to obtain the title compound (18 mg, 8%) as a brown solid.

후처리

  1. extractionthe mixture was extracted with dichloromethane
  2. washthe organic layer was washed with water
  3. dry with materialdried with anhydrous sodium sulfate
  4. distillationThen the solvent was distilled off under reduced pressure
  5. customThe residue was purified by preparative TLC (dichloromethane:methanol=9:1)

출처 및 근거

ORD 기록
ord-fedb12ebcad24dd0b783434e7d72f30e
출처 데이터셋
uspto-grants-2015_01
특허 번호
US08927536B2

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