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 1942799

反応式

HRID 1942799 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+].Cl[C:17]1[CH:22]=[CH:21][N:20]=[C:19]2[CH:23]=[C:24]([C:26]3[N:31]=[CH:30][C:29]([CH2:32][N:33]([CH2:41][CH2:42][O:43][CH3:44])[C:34](=[O:40])[O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[CH:28][CH:27]=3)[S:25][C:18]=12.Cl>CS(C)=O.O.C(Cl)Cl.CCOC(C)=O>[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:17]2[CH:22]=[CH:21][N:20]=[C:19]3[CH:23]=[C:24]([C:26]4[N:31]=[CH:30][C:29]([CH2:32][N:33]([CH2:41][CH2:42][O:43][CH3:44])[C:34](=[O:40])[O:35][C:36]([CH3:37])([CH3:38])[CH3:39])=[CH:28][CH:27]=4)[S:25][C:18]=23)=[CH:4][C:3]=1[F:9]

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 in DMSO (12 mL) was added potassium tert-butoxide (0.824 g, 7.34 mmol). After 30 min, intermediate 145 (2.451 g, 5.65 mmol) was added and the reaction mixture was heated at 100° C. for 1.5 h. It was then cooled down, 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 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 126a (0.952 g, 32% yield). MS (m/z): 525.2 (M+H).

後処理

  1. temperatureIt was then cooled down
  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

出典と根拠

ORDレコード
ord-c4ca534cb8304eb58eca633ec2f0e238
出典データセット
uspto-grants-2013_03
特許番号
US08389541B2

関連ノート

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