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

反応式

HRID 1475543 の反応式
[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]

参加物

9

反応物 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

生成物 1

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

試薬・触媒・溶媒 4

HCID 679Dimethyl Sulfoxide溶媒HCID 962Water溶媒2 回HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
100 °C

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-b7dd0e218fd84aeb880cdd2884dfbf12
出典データセット
uspto-grants-2015_04
特許番号
US09018378B2

関連ノート

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