Methanesulfonamide → 5-Chloro-2-(4-fluorophenoxy)-N-[(1S)-1-(4-{[(methylsulfonyl)amino]carbonyl}phenyl)ethyl]nicotinamide

HRID 1293270

반응식

HRID 1293270 반응식
[Cl:1][C:2]1[CH:3]=[C:4]([C:16]([NH:18][C@H:19]([C:21]2[CH:29]=[CH:28][C:24]([C:25](O)=[O:26])=[CH:23][CH:22]=2)[CH3:20])=[O:17])[C:5]([O:8][C:9]2[CH:14]=[CH:13][C:12]([F:15])=[CH:11][CH:10]=2)=[N:6][CH:7]=1.[CH3:30][S:31]([NH2:34])(=[O:33])=[O:32].Cl.CN(C)CCCN=C=NCC>ClCCl.C(OCC)(=O)C>[Cl:1][C:2]1[CH:7]=[N:6][C:5]([O:8][C:9]2[CH:14]=[CH:13][C:12]([F:15])=[CH:11][CH:10]=2)=[C:4]([CH:3]=1)[C:16]([NH:18][C@H:19]([C:21]1[CH:29]=[CH:28][C:24]([C:25]([NH:34][S:31]([CH3:30])(=[O:33])=[O:32])=[O:26])=[CH:23][CH:22]=1)[CH3:20])=[O:17]

참가 물질

6

반응물 3

HCID 72879MethanesulfonamideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 116830884-[(1S)-1-({[5-Chloro-2-(4-fluorophenoxy)pyridin-3-YL]carbonyl}amino)ethyl]benzoic acid

생성물 1

HCID 589053225-Chloro-2-(4-fluorophenoxy)-N-[(1S)-1-(4-{[(methylsulfonyl)amino]carbonyl}phenyl)ethyl]nicotinamide수율 98.9%

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 8857Ethyl Acetate용매

실험 절차

A mixture of 4-[(1S)-1-({[5-chloro-2-(4-fluorophenoxy)pyridin-3-yl]carbonyl}amino)ethyl]benzoic acid (step 5 of Example 44, 250 mg, 0.60 mmol), methanesulfonamide (60 mg, 0.63 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (139 mg, 0.73 mmol) and dimethylaminopyridiene (78 mg, 0.63 mmol) in dichloromethane (5 mL) was stirred at room temperature overnight. The reaction mixture was diluted with ethyl acetate. The solution was washed with 1M hydrochloric acid, water, and brine, dried over sodium sulfate, and evaporated. The residue was purified by flush column chromatography on silica gel eluting with dichloromethane/methanol (40/1) to afford 292 mg (98%) of the title compound: 1H-NMR (CDCl3) δ 8.52 (1H, d, J=2.8 Hz), 8.14 (1H, d, J=2.8 Hz), 8.16–8.02 (1H, m), 7.81 (2H, d, J=8.3 Hz), 7.46 (2H, d, J=8.3 Hz), 7.23–7.10 (4H, m), 5.44–5.28 (1H, m), 3.41 (3H, s), 1.59 (3H, d, J=7.0 Hz); MS (ESI) m/z 492 (M+H)+, 490 (M−H)−.

후처리

  1. washThe solution was washed with 1M hydrochloric acid, water, and brine
  2. dry with materialdried over sodium sulfate
  3. customevaporated
  4. customThe residue was purified
  5. customby flush column chromatography on silica gel eluting with dichloromethane/methanol (40/1)

출처 및 근거

ORD 기록
ord-2a3657ee6ff24ed794abc1e2bb2fea69
출처 데이터셋
uspto-grants-2007_07
특허 번호
US07238714B2

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