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

HRID 1293270

反応式

HRID 1293270 の反応式
[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]

参加物

6

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒

実験手順

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)−.

後処理

  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)

出典と根拠

ORDレコード
ord-2a3657ee6ff24ed794abc1e2bb2fea69
出典データセット
uspto-grants-2007_07
特許番号
US07238714B2

関連ノート

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