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

HRID 1293270

Reaktionsgleichung

Reaktionsgleichung von HRID 1293270
[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]

Komponenten

6

Edukt 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

Produkt 1

HCID 589053225-Chloro-2-(4-fluorophenoxy)-N-[(1S)-1-(4-{[(methylsulfonyl)amino]carbonyl}phenyl)ethyl]nicotinamideAusbeute 98,9 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

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)−.

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-2a3657ee6ff24ed794abc1e2bb2fea69
Quelldatensatz
uspto-grants-2007_07
Patentnummer
US07238714B2

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