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 2402404Notes

Reaction equation

HRID 2402404 reaction equation
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

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 84468Trifluoroacetate2×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

Product 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 acidYield 30.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
70 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-26e3fcbabad24e878353a4d0df5b56d9
Source dataset
uspto-grants-2014_08
Patent number
US08796310B2

Reaction notes

Loading…