Triethylamine → [5-(4-Methoxyphenyl)-1,3,4-oxadiazol-2-yl]-[3-[4-(2-oxa-7-azaspiro[4.4]nonan-7-ylmethyl)phenoxy]azetidin-1-yl]methanone

HRID 2359367Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2359367
Cl.[CH2:2]1[C:6]2([CH2:10][CH2:9][NH:8][CH2:7]2)[CH2:5][CH2:4][O:3]1.C(N(CC)CC)C.[CH3:18][O:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]2[O:30][C:29]([C:31]([N:33]3[CH2:36][CH:35]([O:37][C:38]4[CH:45]=[CH:44][C:41]([CH:42]=O)=[CH:40][CH:39]=4)[CH2:34]3)=[O:32])=[N:28][N:27]=2)=[CH:22][CH:21]=1.[Na].C([O-])(O)=O.[Na+]>ClCCl>[CH2:2]1[C:6]2([CH2:10][CH2:9][N:8]([CH2:42][C:41]3[CH:40]=[CH:39][C:38]([O:37][CH:35]4[CH2:36][N:33]([C:31]([C:29]5[O:30][C:26]([C:23]6[CH:24]=[CH:25][C:20]([O:19][CH3:18])=[CH:21][CH:22]=6)=[N:27][N:28]=5)=[O:32])[CH2:34]4)=[CH:45][CH:44]=3)[CH2:7]2)[CH2:5][CH2:4][O:3]1

Komponenten

7

Edukt 5

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 5360545SodiumHCID 580430894-(1-(5-(4-Methoxyphenyl)-1,3,4-oxadiazole-2-carbonyl)azetidin-3-yloxy)benzaldehydeHCID 717438382-Oxa-7-azaspiro[4.4]nonane hydrochloride

Produkt 1

HCID 71226697[5-(4-Methoxyphenyl)-1,3,4-oxadiazol-2-yl]-[3-[4-(2-oxa-7-azaspiro[4.4]nonan-7-ylmethyl)phenoxy]azetidin-1-yl]methanoneAusbeute 46,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

2-Oxa-7-azaspiro[4.4]nonane HCl salt (0.057 g, 0.35 mmol) was dissolved in dichloromethane (2 ml). To the resulting solution was added triethylamine (0.052 ml, 0.38 mmol), followed by 4-(1-(5-(4-methoxyphenyl)-1,3,4-oxadiazole-2-carbonyl)azetidin-3-yloxy)benzaldehyde (0.11 g, 0.29 mmol) and sodium triacetoxyhydroborate (0.123 g, 0.58 mmol). The mixture was stirred at ambient temperature overnight. The reaction mixture was then diluted with dichloromethane (10 ml) and shaken with NaHCO3 (sat. 2 ml). The two phases were separated using a phase separator. The organic phase was evaporated. The product was purified by preparative reverse-phase HPLC at pH 10 to give 0.066 g (46%) of the desired product as a solid. 1H NMR (400 MHz, CDCl3) δ 1.92 (ddd 4H), 2.42 (d, 1H), 2.62 (dd, 3H), 3.58 (d, 3H), 3.71 (d, 1H), 3.84 (ddd, 2H), 3.92 (s, 3H), 4.35 (d, 1H), 4.67 (dd, 1H), 4.77 (d, 1H), 5.04-5.19 (m, 2H), 6.75 (d, 2H), 7.05 (d, 2H), 7.29 (d, 2H), 8.12 (d, 2H). MS (APCI+) m/z 491.3 [M+H]+, LC purity: 97%

Aufarbeitung

  1. customThe two phases were separated
  2. customThe organic phase was evaporated
  3. customThe product was purified by preparative reverse-phase HPLC at pH 10

Quellen und Nachweise

ORD-Eintrag
ord-d1a0ea64a63b43ccb3180cc5fa7e1bb0
Quelldatensatz
uspto-grants-2014_04
Patentnummer
US08685958B2

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