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

HRID 2359370노트

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HRID 2359370 반응식
[C:1]1([C:7]2[O:11][C:10]([C:12]([N:14]3[CH2:17][CH:16]([O:18][C:19]4[CH:26]=[CH:25][C:22]([CH:23]=O)=[CH:21][CH:20]=4)[CH2:15]3)=[O:13])=[N:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(CC)CC)C.Cl.[CH2:35]1[C:39]2([CH2:43][CH2:42][NH:41][CH2:40]2)[CH2:38][CH2:37][O:36]1.[Na].C([O-])(O)=O.[Na+]>ClCCl>[CH2:35]1[C:39]2([CH2:43][CH2:42][N:41]([CH2:23][C:22]3[CH:21]=[CH:20][C:19]([O:18][CH:16]4[CH2:15][N:14]([C:12]([C:10]5[O:11][C:7]([C:1]6[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=6)=[N:8][N:9]=5)=[O:13])[CH2:17]4)=[CH:26][CH:25]=3)[CH2:40]2)[CH2:38][CH2:37][O:36]1

참가 물질

7

반응물 5

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 5360545SodiumHCID 58043115HCID 58043115, 화합물HCID 717438382-Oxa-7-azaspiro[4.4]nonane hydrochloride

생성물 1

HCID 71225843(3-(4-(2-Oxa-7-azaspiro[4.4]nonan-7-ylmethyl)phenoxy)azetidin-1-yl)(5-phenyl-1,3,4-oxadiazol-2-yl)methanone수율 81.4%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To a solution of 4-(1-(5-phenyl-1,3,4-oxadiazole-2-carbonyl)azetidin-3-yloxy)benzaldehyde (70 mg, 0.20 mmol) in dichloromethane (2 mL) was added triethylamine (0.100 mL, 0.72 mmol) and 2-oxa-7-azaspiro[4.4]nonane hydrochloride (77 mg, 0.47 mmol). The resulting mixture was stirred for 30 minutes at ambient temperature, after which was added sodium triacetoxyhydroborate (114 mg, 0.54 mmol). Stirring was continued at ambient temperature overnight, after which NaHCO3 (aq, sat, 5 ml) was added to the reaction mixture. The phases were separated using a phase separator. The aqueous phase was extracted twice with dichloromethane and dried with the aid of a phase separator. The combined organic phases were concentrated in vacuo to afford a colourless residue weighing 112 mg. The crude material was purified by preparative reverse-phase HPLC at pH 10 to give 75 mg (81%) of the desired product as a solid. 1H NMR (600 MHz, CDCl3): δ 1.75 (t, 2H), 1.79-1.89 (m, 2H), 2.32 (d, 1H), 2.45-2.49 (m, 2H), 2.59 (dd, 1H), 3.43 (d, 1H), 3.48-3.56 (m, 3H), 3.63-3.75 (m, 2H), 4.10 (dd, 1H), 4.56 (dd, 1H), 4.61-4.67 (m, 1H), 5.10 (dd, 1H), 5.16 (ddd, 1H), 6.86 (d, 2H), 7.26 (d, 2H), 7.63-7.73 (m, 3H), 8.06-8.11 (m, 2H). MS (APCI+) m/z 461.2 [M+H]+, LC purity: 97%

후처리

  1. stirringStirring
  2. waitwas continued at ambient temperature overnight
  3. customThe phases were separated
  4. extractionThe aqueous phase was extracted twice with dichloromethane
  5. customdried with the aid of a phase separator
  6. concentrationThe combined organic phases were concentrated in vacuo
  7. customto afford a colourless residue
  8. customThe crude material was purified by preparative reverse-phase HPLC at pH 10

출처 및 근거

ORD 기록
ord-902fb45d7215442d896b0b13d08e7d29
출처 데이터셋
uspto-grants-2014_04
특허 번호
US08685958B2

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