Sodium Hydroxide → 5-Amino-5-(5-(4-methyl-6-((4-(trifluoromethyl)pyridine-2-yl)amino)pyridine-2-yl)thiazol-2-yl)-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid

HRID 2402404ノート

反応式

HRID 2402404 の反応式
FC(F)(F)C([O-])=O.[NH2:8][C:9]1([C:23]2[S:24][C:25]([C:28]3[CH:33]=[C:32]([CH3:34])[CH:31]=[C:30]([NH:35][C:36]4[CH:41]=[C:40]([C:42]([F:45])([F:44])[F:43])[CH:39]=[CH:38][N:37]=4)[N:29]=3)=[CH:26][N:27]=2)[CH2:18][CH2:17][CH2:16][C:15]2[CH:14]=[C:13]([C:19]([O:21]C)=[O:20])[CH:12]=[CH:11][C:10]1=2.[OH-].[Na+]>CCO>[NH2:8][C:9]1([C:23]2[S:24][C:25]([C:28]3[CH:33]=[C:32]([CH3:34])[CH:31]=[C:30]([NH:35][C:36]4[CH:41]=[C:40]([C:42]([F:43])([F:45])[F:44])[CH:39]=[CH:38][N:37]=4)[N:29]=3)=[CH:26][N:27]=2)[CH2:18][CH2:17][CH2:16][C:15]2[CH:14]=[C:13]([C:19]([OH:21])=[O:20])[CH:12]=[CH:11][C:10]1=2

参加物

5

反応物 3

HCID 14798Sodium HydroxideHCID 84468Trifluoroacetate2 回HCID 71002247Methyl 5-amino-5-(5-(4-methyl-6-((4-(trifluoromethyl)pyridin-2-yl)amino)pyridin-2-yl)thiazol-2-yl)-5,6,7,8-tetrahydronaphthalene-2-carboxylate

生成物 1

HCID 709779105-Amino-5-(5-(4-methyl-6-((4-(trifluoromethyl)pyridine-2-yl)amino)pyridine-2-yl)thiazol-2-yl)-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid収率 30.2%

試薬・触媒・溶媒 1

HCID 702Ethanol溶媒

反応条件

温度
70 °C

実験手順

To a solution of the trifluoroacetate salt of methyl 5-amino-5-(5-(4-methyl-6-((4-(trifluoromethyl)pyridin-2-yl)amino)pyridin-2-yl)thiazol-2-yl)-5,6,7,8-tetrahydronaphthalene-2-carboxylate (30 mg, 0.056 mmol) in EtOH (2 mL) was added sodium hydroxide (1 mL, 2.000 mmol) and the mixture was stirred at 70° C. for 45 min. The organic solvent was then removed under reduced pressure, and the residue was diluted with water, neutralized with 2N HCl (˜1 mL), then extracted with EtOAc, dried over Na2SO4, and filtered. The filtrate was concentrated under reduced pressure, then purified by reverse phase chromatography using a C18 column with a mobile phase of MeCN and water modified with 0.1% TFA. The product containing fractions were combined and lyophilized the trifluoroacetate salt of 5-amino-5-(5-(4-methyl-6-((4-(trifluoromethyl)pyridine-2-yl)amino)pyridine-2-yl)thiazol-2-yl)-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid as white solid (8.9 mg, 25% yield). MS ESI calcd for C26H22F3N5O2S [M+H]+ 526, found 526. 1H NMR (600 MHz, cd3od) δ 8.47 (s, 1H), 8.40 (s, 1H), 8.34 (d, J=5.2, 1H), 8.02 (s, 1H), 7.94 (d, J=8.2, 1H), 7.55 (d, J=8.3, 1H), 7.32 (s, 1H), 7.03 (d, J=5.1, 1H), 6.90 (s, 1H), 3.06 (t, J=6.1, 2H), 2.72-2.59 (m, 1H), 2.46-2.38 (m, 1H), 2.34 (s, 3H), 2.07 (s, 1H), 2.01-1.90 (m, 1H).

後処理

  1. customThe organic solvent was then removed under reduced pressure
  2. additionthe residue was diluted with water
  3. extractionextracted with EtOAc
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. custompurified by reverse phase chromatography
  8. additionThe product containing fractions

出典と根拠

ORDレコード
ord-26e3fcbabad24e878353a4d0df5b56d9
出典データセット
uspto-grants-2014_08
特許番号
US08796310B2

反応ノート

読み込み中…