1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 4-((1-benzoylazetidin-3-yl)methoxy)-5-cyclopropyl-2-fluoro-N-(methylsulfonyl)benzamide

HRID 1849893Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1849893
[C:1]([N:9]1[CH2:12][CH:11]([CH2:13][O:14][C:15]2[C:23]([CH:24]3[CH2:26][CH2:25]3)=[CH:22][C:18]([C:19](O)=[O:20])=[C:17]([F:27])[CH:16]=2)[CH2:10]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCN=C=NCCCN(C)C.[CH3:39][S:40]([NH2:43])(=[O:42])=[O:41]>CN(C1C=CN=CC=1)C.C(Cl)Cl>[C:1]([N:9]1[CH2:12][CH:11]([CH2:13][O:14][C:15]2[C:23]([CH:24]3[CH2:26][CH2:25]3)=[CH:22][C:18]([C:19]([NH:43][S:40]([CH3:39])(=[O:42])=[O:41])=[O:20])=[C:17]([F:27])[CH:16]=2)[CH2:10]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Komponenten

6

Edukt 3

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 72879MethanesulfonamideHCID 867037714-((1-Benzoylazetidin-3-yl)methoxy)-5-cyclopropyl-2-fluorobenzoic acid

Produkt 1

HCID 725493564-((1-benzoylazetidin-3-yl)methoxy)-5-cyclopropyl-2-fluoro-N-(methylsulfonyl)benzamideAusbeute 17,9 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

A mixture of 4-((1-benzoylazetidin-3-yl)methoxy)-5-cyclopropyl-2-fluorobenzoic acid (20 mg, 0.05 mmol), EDCI (21 mg, 0.10 mmol), DMAP (12 mg, 0.10 mmol) and methanesulfonamide (9 mg, 0.10 mmol) in DCM (5 mL) was stirred at room temperature for 18 h. The mixture was diluted with DCM (10 mL) and washed with HCl (2 N, 15 mL×2). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by HPLC (20%-30% CH3CN in 0.1% NH4HCO3) to give target compound (4 mg, 17%) as a pale yellow solid. LCMS (ESI) Method A: RT=3.86 min, m/z: 446.5 [M+H]+. 1H-NMR (500 MHz, MeOH-d4,): δ 7.67-7.31 (m, 5H), 7.30 (d, J=8.5 Hz, 1H), 6.89 (d, J=13.0 Hz, 1H), 4.65-3.62 (m, 1H), 4.61-4.22 (m, 5H), 3.36 (s, 3H), 3.25-3.23 (m, 1H), 1.99-1.95 (m, 1H), 0.94-0.61 (m, 4H).

Aufarbeitung

  1. washwashed with HCl (2 N, 15 mL×2)
  2. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified by HPLC (20%-30% CH3CN in 0.1% NH4HCO3)

Quellen und Nachweise

ORD-Eintrag
ord-f93f6b6c6134431bb4cb2534c4bea48d
Quelldatensatz
uspto-grants-2015_02
Patentnummer
US08952169B2

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