Triethylamine → (3-(4-(2-Oxa-5-azaspiro[3.4]octan-5-ylmethyl)phenoxy)azetidin-1-yl)(5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl)methanone

HRID 2359376노트

반응식

HRID 2359376 반응식
[CH2:1]1[C:4]2([CH2:8][CH2:7][CH2:6][NH:5]2)[CH2:3][O:2]1.C(N(CC)CC)C.[CH3:16][O:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]2[O:28][C:27]([C:29]([N:31]3[CH2:34][CH:33]([O:35][C:36]4[CH:43]=[CH:42][C:39]([CH:40]=O)=[CH:38][CH:37]=4)[CH2:32]3)=[O:30])=[N:26][N:25]=2)=[CH:20][CH:19]=1.[Na].C([O-])(O)=O.[Na+]>ClCCl>[CH2:3]1[C:4]2([CH2:8][CH2:7][CH2:6][N:5]2[CH2:40][C:39]2[CH:38]=[CH:37][C:36]([O:35][CH:33]3[CH2:34][N:31]([C:29]([C:27]4[O:28][C:24]([C:21]5[CH:22]=[CH:23][C:18]([O:17][CH3:16])=[CH:19][CH:20]=5)=[N:25][N:26]=4)=[O:30])[CH2:32]3)=[CH:43][CH:42]=2)[CH2:1][O:2]1

참가 물질

7

반응물 5

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 5360545SodiumHCID 547591262-Oxa-5-azaspiro(3.4)octaneHCID 580430894-(1-(5-(4-Methoxyphenyl)-1,3,4-oxadiazole-2-carbonyl)azetidin-3-yloxy)benzaldehyde

생성물 1

HCID 71227161(3-(4-(2-Oxa-5-azaspiro[3.4]octan-5-ylmethyl)phenoxy)azetidin-1-yl)(5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl)methanone수율 60.5%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

2-Oxa-5-azaspiro[3.4]octane (0.03 g, 0.26 mmol) was dissolved in dichloromethane (2 ml). Triethylamine (0.04 ml, 0.29 mmol) was added, followed by 4-(1-(5-(4-methoxyphenyl)-1,3,4-oxadiazole-2-carbonyl)azetidin-3-yloxy)benzaldehyde (0.1 g, 0.26 mmol) and finally sodium triacetoxyhydroborate (0.112 g, 0.53 mmol). The mixture was stirred at ambient temperature overnight. The reaction mixture was then diluted with dichloromethane (10 ml) and subsequently shaken with NaHCO3 (sat. 3 ml). The two phases were separated by the use of a phase separator. Evaporation of the organic phase afforded a residue, which was purified by preparative reverse-phase. HPLC at pH 10 to give 0.075 g (60%) of the desired product as a solid. 1H NMR (600 MHz, DMSO) δ 1.62 (dt, 2H), 2.1-2.15 (m, 2H), 2.49 (t, 2H), 3.88 (s, 3H), 3.91 (s, 2H), 4.09 (ddd, 1H), 4.43 (d, 2H), 4.54 (ddd, 1H), 4.63 (ddd, 1H), 4.80 (d, 2H), 5.09 (ddd, 1H), 5.16 (ddd, 1H), 6.86 (d, 2H), 7.17-7.21 (m, 2H), 7.30 (d, 2H), 8-8.04 (m, 2H). MS (APCI+) m/z 477.2 [M+H]+, LC purity: 95%

후처리

  1. customThe two phases were separated by the use of a phase separator
  2. customEvaporation of the organic phase
  3. customafforded a residue, which
  4. customwas purified by preparative reverse-phase

출처 및 근거

ORD 기록
ord-0895c2be782846969eebc7c5425f0769
출처 데이터셋
uspto-grants-2014_04
특허 번호
US08685958B2

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