[2-(benzyloxy)-5-((1R)-2-bromo-1-{[tert-butyl(dimethyl)silyl]oxy}ethyl)phenyl]methanol → Ammonia

HRID 1433292노트

반응식

HRID 1433292 반응식
Cl.Cl.C([N:7](CCC1C=CC(OCCCCC2C=CC(O)=C([C@@H](C3C=CC=CC=3)CCN(C(C)C)C(C)C)C=2)=CC=1)C([O:10][C:11]1[CH:16]=[CH:15][C:14]([CH2:17][CH2:18][CH2:19][CH2:20][O:21][C:22]2[CH:27]=[CH:26][C:25]([CH2:28][CH2:29][NH2:30])=[CH:24][CH:23]=2)=[CH:13][C:12]=1[C@@H:31]([C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)[CH2:32][CH2:33][N:34]([CH:38]([CH3:40])[CH3:39])[CH:35]([CH3:37])[CH3:36])=O)(C)(C)C.[CH2:83]([O:90][C:91]1[CH:96]=[CH:95][C:94]([C@@H:97]([O:100][Si:101]([C:104]([CH3:107])([CH3:106])[CH3:105])([CH3:103])[CH3:102])[CH2:98]Br)=[CH:93][C:92]=1[CH2:108][OH:109])[C:84]1[CH:89]=[CH:88][CH:87]=[CH:86][CH:85]=1>C(=O)([O-])O.[Na+].ClCCl>[NH3:7].[CH2:83]([O:90][C:91]1[CH:96]=[CH:95][C:94]([C@@H:97]([O:100][Si:101]([C:104]([CH3:107])([CH3:106])[CH3:105])([CH3:103])[CH3:102])[CH2:98][NH:30][CH2:29][CH2:28][C:25]2[CH:24]=[CH:23][C:22]([O:21][CH2:20][CH2:19][CH2:18][CH2:17][C:14]3[CH:15]=[CH:16][C:11]([OH:10])=[C:12]([C@@H:31]([C:41]4[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=4)[CH2:32][CH2:33][N:34]([CH:35]([CH3:36])[CH3:37])[CH:38]([CH3:40])[CH3:39])[CH:13]=3)=[CH:27][CH:26]=2)=[CH:93][C:92]=1[CH2:108][OH:109])[C:84]1[CH:89]=[CH:88][CH:87]=[CH:86][CH:85]=1

참가 물질

6

반응물 2

HCID 12988834[2-(benzyloxy)-5-((1R)-2-bromo-1-{[tert-butyl(dimethyl)silyl]oxy}ethyl)phenyl]methanolHCID 1317277264-{4-[4-(2-aminoethyl)phenoxy]butyl}-2-[(1R)-3-(diisopropylamino)-1-phenylpropyl]phenol tert-butyl {2-[4-(4-{3-[(1R)-3-(diisopropylamino)-1-phenylpropyl]-4-hydroxyphenyl}butoxy)phenyl]ethyl}carbamate bis hydrochloride salt

생성물 2

HCID 222AmmoniaHCID 579331564-{4-[4-(2-{[(2R)-2-[4-(benzyloxy)-3-(hydroxymethyl)phenyl]-2-{[tert-butyl(dimethyl)silyl]oxy}ethyl]amino}ethyl)phenoxy]butyl}-2-[(1R)-3-(diisopropylamino)-1-phenylpropyl]phenol

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 516892Sodium Bicarbonate용매2회

반응 조건

온도
85 °C

실험 절차

4-{4-[4-(2-aminoethyl)phenoxy]butyl}-2-[(1R)-3-(diisopropylamino)-1-phenylpropyl]phenol tert-butyl{2-[4-(4-{3-[(1R)-3-(diisopropylamino)-1-phenylpropyl]-4-hydroxyphenyl}butoxy)phenyl]ethyl}carbamate bis hydrochloride salt (Preparation 13, 1.30 g, 2.26 mmol), was dissolved in a mixture of saturated aqueous sodium hydrogen carbonate and dichloromethane. The organic layer was separated, dried (magnesium sulphate) and the solvent removed in vacuo The residue was dissolved in acetonitrile (10 ml) and {2-(benzyloxy)-5-[(1R)-2-bromo-1-{[tert-butyl(dimethyl)silyl]oxy}ethyl]phenyl}methanol (Prepared according to WO2004/032921, 1.02 mg, 2.26 mmol), sodium hydrogen carbonate (570 mg, 6.78 mmol) were added, and heated to 85° C. and stirred overnight. After cooling the solvent was removed in vacuo and the residue was dissolved in dichloromethane (30 ml) and washed with water (2×20 ml) then brine (20 ml), dried (magnesium sulphate) and the solvent removed in vacuo. The residue was purified by column chromatography on silica gel eluting with dichloromethane:methanol:880 ammonia (95/5/1 to 90/10/1 by volume) to furnish the title compound as a gum, 388 mg.

후처리

  1. customThe organic layer was separated
  2. dry with materialdried (magnesium sulphate)
  3. customthe solvent removed in vacuo The residue
  4. dissolutionwas dissolved in acetonitrile (10 ml)
  5. temperatureAfter cooling the solvent
  6. customwas removed in vacuo
  7. dissolutionthe residue was dissolved in dichloromethane (30 ml)
  8. washwashed with water (2×20 ml)
  9. dry with materialbrine (20 ml), dried (magnesium sulphate)
  10. customthe solvent removed in vacuo
  11. customThe residue was purified by column chromatography on silica gel eluting with dichloromethane

출처 및 근거

ORD 기록
ord-0964138489f645d0a49a6f165cd09d5f
출처 데이터셋
uspto-grants-2009_11
특허 번호
US07612084B2

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