(3-Methoxyphenyl)boronic acid → ethyl 3-(2-(3-methoxyphenyl)-2,3-dihydro-1H-spiro[isoquinoline-4,4'-piperidine]-1'-yl)-8-azabicyclo[3.2.1]octane-8-carboxylate

HRID 251487노트

반응식

HRID 251487 반응식
[CH3:1][O:2][C:3]1[CH:4]=[C:5](B(O)O)[CH:6]=[CH:7][CH:8]=1.Cl.[N:13]1([CH:28]2[CH2:34][CH:33]3[N:35]([C:36]([O:38][CH2:39][CH3:40])=[O:37])[CH:30]([CH2:31][CH2:32]3)[CH2:29]2)[CH2:18][CH2:17][C:16]2([C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[CH2:21][NH:20][CH2:19]2)[CH2:15][CH2:14]1>C(Cl)Cl.CO>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([N:20]2[CH2:19][C:16]3([CH2:17][CH2:18][N:13]([CH:28]4[CH2:29][CH:30]5[N:35]([C:36]([O:38][CH2:39][CH3:40])=[O:37])[CH:33]([CH2:32][CH2:31]5)[CH2:34]4)[CH2:14][CH2:15]3)[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[CH2:21]2)[CH:6]=[CH:7][CH:8]=1

참가 물질

5

반응물 2

HCID 2734370(3-Methoxyphenyl)boronic acidHCID 86609340Ethyl 3-(2,3-dihydro-1H-spiro[isoquinoline-4,4'-piperidine]-1'-yl)-8-azabicyclo[3.2.1]octane-8-carboxylate hydrochloride

생성물 1

HCID 58089606ethyl 3-(2-(3-methoxyphenyl)-2,3-dihydro-1H-spiro[isoquinoline-4,4'-piperidine]-1'-yl)-8-azabicyclo[3.2.1]octane-8-carboxylate

시약·촉매·용매 2

HCID 887Methanol용매HCID 6344Dichloromethane용매

실험 절차

A suspension of 3-methoxyphenylboronic acid (30 mg, 0.2 mmol), Cu(OAc)2H2O (2 mg, 5 mol %), 3 Å molecular sieves (75 mg) in 1 mL of CH2Cl2 were stirred at room temperature for 5 min. Ethyl 3-(2,3-dihydro-1H-spiro[isoquinoline-4,4′-piperidine]-1′-yl)-8-azabicyclo[3.2.1]octane-8-carboxylate hydrochloride 5c (42 mg, 0.1 mmol) was added to the reaction and mixture was stirred at room temperature for 24 h. The reaction was diluted with methanol, filtered and subjected to reverse-phase HPLC purification (2-50% CH3CN—H2O gradient, with 0.05% TFA, 15 min) to give pure ethyl 3-(2-(3-methoxyphenyl)-2,3-dihydro -1H-spiro[isoquinoline-4,4′-piperidine]-1′-yl)-8-azabicyclo[3.2.1]octane-8-carboxylate. LC-MS: m/z [M+H]+ 490.0, retention time 2.61 min (10-90% CH3CN—H2O gradient, with 0.05% TFA, 5 min).

후처리

  1. stirringwas stirred at room temperature for 24 h
  2. filtrationfiltered
  3. customsubjected to reverse-phase HPLC purification (2-50% CH3CN—H2O gradient, with 0.05% TFA, 15 min)

출처 및 근거

ORD 기록
ord-a739371959384828a889782a7d27947f
출처 데이터셋
uspto-grants-2011_01
특허 번호
US07863449B2

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