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 2359367ノート

反応式

HRID 2359367 の反応式
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

参加物

7

反応物 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

生成物 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]methanone収率 46.4%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

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%

後処理

  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

出典と根拠

ORDレコード
ord-d1a0ea64a63b43ccb3180cc5fa7e1bb0
出典データセット
uspto-grants-2014_04
特許番号
US08685958B2

反応ノート

読み込み中…