Triethylamine → 1-{1-[(3S)-4-[[3-Bromo-5-(trifluoromethyl)benzoyl](methyl)amino]-3-(4-fluorophenyl)butyl]azetidin-3-yl}piperidine-4-carboxamide

HRID 426079Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 426079
[N:1]1([C:5]([CH:7]2[CH2:12][CH2:11][N:10]([CH:13]3[CH2:16][N:15]([CH2:17][CH2:18][C@@H:19]([C:36]4[CH:41]=[CH:40][C:39]([F:42])=[CH:38][CH:37]=4)[CH2:20][N:21]([CH3:35])[C:22](=[O:34])[C:23]4[CH:28]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:26]=[C:25]([Br:33])[CH:24]=4)[CH2:14]3)[CH2:9][CH2:8]2)=[O:6])CCC1.N1CC(N2CCC(C(N)=O)CC2)C1.C(N(CC)CC)C.C([BH3-])#N.[Na+]>C(Cl)Cl.CO>[Br:33][C:25]1[CH:24]=[C:23]([CH:28]=[C:27]([C:29]([F:31])([F:30])[F:32])[CH:26]=1)[C:22]([N:21]([CH3:35])[CH2:20][C@H:19]([C:36]1[CH:41]=[CH:40][C:39]([F:42])=[CH:38][CH:37]=1)[CH2:18][CH2:17][N:15]1[CH2:14][CH:13]([N:10]2[CH2:11][CH2:12][CH:7]([C:5]([NH2:1])=[O:6])[CH2:8][CH2:9]2)[CH2:16]1)=[O:34]

Komponenten

7

Edukt 4

HCID 8471TriethylamineHCID 5003444Sodium cyanoborohydrideHCID 23582759N-[(2S)-4-{3-[4-(Azetidin-1-ylcarbonyl)piperidin-1-yl]azetidin-1-yl}-2-(4-fluorophenyl)butyl]-3-bromo-N-methyl-5-(trifluoromethyl)benzamideHCID 236589541-Azetidin-3-ylpiperidine-4-carboxamide

Produkt 1

HCID 236615481-{1-[(3S)-4-[[3-Bromo-5-(trifluoromethyl)benzoyl](methyl)amino]-3-(4-fluorophenyl)butyl]azetidin-3-yl}piperidine-4-carboxamideAusbeute 17,5 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

3-Bromo-N-[(2S)-2-(4-fluorophenyl)-4-oxobutyl]-N-methyl-5-(trifluoromethyl)benzamide (see method 1; 1.00 g, 2.24 mmol) and 1-azetidin-3-ylpiperidine-4-carboxamide (see method 4; 0.49 g, 2.69 mmol) and triethylamine (1.24 mL, 9.0 mmol) were dissolved in methylene chloride (30 mL) together with methanol (5 mL). To the resultant solution was added sodium cyanoborohydride (0.21 g, 3.36 mmol) and the mixture was stirred at RT for 20 min. The solvent was removed by evaporation and the residue was partitioned between methylene chloride and saturated aqueous NaHCO3. The organic phase was filtered through a phase separator and the solvent was removed by evaporation. The product was purified by chromatography on silica gel (ammonia saturated methanol/methylene chloride, 1-20% methanol). There was obtained 0.24 g (17%) of the title compound. 1H NMR (500 MHz, CDCl3): δ 1.4-3.8 (cm, 23H), 5.7 (b, 1H), 5.8 (b, 1H), 6.8-7.4 (cm, 6H), 7.7 (s, 1H); LCMS: m/z 614 (M+1)+.

Aufarbeitung

  1. customThe solvent was removed by evaporation
  2. customthe residue was partitioned between methylene chloride and saturated aqueous NaHCO3
  3. filtrationThe organic phase was filtered through a phase separator
  4. customthe solvent was removed by evaporation
  5. customThe product was purified by chromatography on silica gel (ammonia saturated methanol/methylene chloride, 1-20% methanol)

Quellen und Nachweise

ORD-Eintrag
ord-e736d21716bc447787b10d96386f3a93
Quelldatensatz
uspto-grants-2012_01
Patentnummer
US08106208B2

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