Hydrochloric Acid → tert-Butyl (6-(7-(4-amino-3-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)pyridin-3-yl)methyl(2-methoxyethyl)carbamate

HRID 1475543

반응식

HRID 1475543 반응식
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][C:3]=1[F:9].CC(C)([O-])C.[K+].[C:16]([O:20][C:21](=[O:44])[N:22]([CH2:27][C:28]1[CH:29]=[N:30][C:31]([C:34]2[S:42][C:41]3[C:36](=[N:37][CH:38]=[CH:39][C:40]=3Cl)[CH:35]=2)=[CH:32][CH:33]=1)[CH2:23][CH2:24][O:25][CH3:26])([CH3:19])([CH3:18])[CH3:17].Cl>CS(C)=O.O.C(Cl)Cl.CCOC(C)=O>[C:16]([O:20][C:21](=[O:44])[N:22]([CH2:27][C:28]1[CH:29]=[N:30][C:31]([C:34]2[S:42][C:41]3[C:36](=[N:37][CH:38]=[CH:39][C:40]=3[O:8][C:5]3[CH:6]=[CH:7][C:2]([NH2:1])=[C:3]([F:9])[CH:4]=3)[CH:35]=2)=[CH:32][CH:33]=1)[CH2:23][CH2:24][O:25][CH3:26])([CH3:19])([CH3:17])[CH3:18]

참가 물질

9

반응물 4

HCID 313Hydrochloric AcidHCID 27359194-Amino-3-fluorophenolHCID 23665647Potassium tert-butoxideHCID 57919613tert-Butyl ((6-(7-chlorothieno[3,2-b]pyridin-2-yl)pyridin-3-yl)methyl)(2-methoxyethyl)carbamate

생성물 1

HCID 57919486tert-Butyl (6-(7-(4-amino-3-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)pyridin-3-yl)methyl(2-methoxyethyl)carbamate수율 32%

시약·촉매·용매 4

HCID 679Dimethyl Sulfoxide용매HCID 962Water용매2회HCID 6344Dichloromethane용매HCID 8857Ethyl Acetate용매

반응 조건

온도
100 °C

실험 절차

To a solution of 4-amino-3-fluorophenol (19) in DMSO (12 mL) was added potassium tert-butoxide (0.824 g, 7.34 mmol). After 30 min, intermediate 11 (2.451 g, 5.65 mmol) was added and the reaction mixture was heated at 100° C. for 1.5 h, cooled to room temperature, poured in water (50 mL) at 40-45° C. and stirred for 30 min. EtOAc (40 mL), DCM (40 mL) and water (40 ml) were added and the pH was adjusted to 7 by addition of HCl. Solids were removed by filtration through a paper filter and the two phases were separated. The organic layer was collected, dried over anhydrous Na2SO4, filtered and concentrated. The residue was purified by flash column chromatography (eluent DCM/MeOH: 99/1, 98/2, 95/5), to afford intermediate 20 (0.952 g, 32% yield). MS (m/z): 525.2 (M+H).

후처리

  1. temperaturecooled to room temperature
  2. customSolids were removed by filtration through a paper
  3. filtrationfilter
  4. customthe two phases were separated
  5. customThe organic layer was collected
  6. dry with materialdried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by flash column chromatography (eluent DCM/MeOH: 99/1, 98/2, 95/5)

출처 및 근거

ORD 기록
ord-b7dd0e218fd84aeb880cdd2884dfbf12
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09018378B2

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