Sodium Bicarbonate → (3-(4-((3-(Hydroxymethyl)-3-methylpyrrolidin-1-yl)methyl)phenoxy)azetidin-1-yl)(5-phenyl-1,3,4-oxadiazol-2-yl)methanone

HRID 1035258노트

반응식

HRID 1035258 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.Cl.[CH3:28][C:29]1([CH2:34][OH:35])[CH2:33][CH2:32][NH:31][CH2:30]1.[Na].C([O-])(O)=O.[Na+]>ClCCl>[OH:35][CH2:34][C:29]1([CH3:28])[CH2:33][CH2:32][N:31]([CH2:23][C:22]2[CH:21]=[CH:20][C:19]([O:18][CH:16]3[CH2:15][N:14]([C:12]([C:10]4[O:11][C:7]([C:1]5[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=5)=[N:8][N:9]=4)=[O:13])[CH2:17]3)=[CH:26][CH:25]=2)[CH2:30]1

참가 물질

6

반응물 4

HCID 516892Sodium BicarbonateHCID 5360545SodiumHCID 58043115HCID 58043115, 화합물HCID 66653455(3-Methylpyrrolidin-3-yl)methanol hydrochloride

생성물 1

HCID 56599063(3-(4-((3-(Hydroxymethyl)-3-methylpyrrolidin-1-yl)methyl)phenoxy)azetidin-1-yl)(5-phenyl-1,3,4-oxadiazol-2-yl)methanone

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

Intermediate 71A (0.15 g, 0.43 mmol), intermediate 84A (0.098 g, 0.64 mmol) and TEA (0.238 mL, 1.72 mmol) were mixed in dichloromethane (4 mL). The mixture was stirred at RT for 30 min and then sodium triacetoxyhydroborate (0.182 g, 0.86 mmol) was added and the mixture was stirred at RT overnight. Aqueous NaHCO3 (sat., 4 mL) and dichloromethane (4 mL) were added and the mixture was filtered through a phase separator and the solvent was removed by evaporation. The product was purified by preparative reverse-phase HPLC at pH 10 to give 21 mg (11%). 1H NMR (600 MHz, DMSO) δ 1.00 (s, 3H), 1.3-1.39 (m, 1H), 1.57-1.64 (m, 1H), 2.05 (d, 1H), 2.41-2.48 (m, 2H), 3.14-3.24 (m, 2H), 3.43-3.51 (m, 2H), 4.07-4.14 (m, 1H), 4.54-4.73 (m, 3H), 5.07-5.19 (m, 2H), 6.85 (d, 2H), 7.25 (d, 2H), 7.63-7.73 (m, 3H), 8.09 (d, 2H), LC purity: 94%.

후처리

  1. stirringthe mixture was stirred at RT overnight
  2. filtrationthe mixture was filtered through a phase separator
  3. customthe solvent was removed by evaporation
  4. customThe product was purified by preparative reverse-phase HPLC at pH 10
  5. customto give 21 mg (11%)

출처 및 근거

ORD 기록
ord-f7ba6f0e89264227ba39c206ace23749
출처 데이터셋
uspto-grants-2013_10
특허 번호
US08546375B2

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