Tetrahydrofuran → (Rac)-5-hydroxy-5-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid, trifluoroacetate salt

HRID 2402393Notes

Reaction equation

HRID 2402393 reaction equation
[OH:1][C:2]1([C:16]2[S:17][C:18]([C:21]3[CH:26]=[C:25]([CH3:27])[CH:24]=[C:23]([NH:28][C:29]4[CH:34]=[C:33]([C:35]([F:38])([F:37])[F:36])[CH:32]=[CH:31][N:30]=4)[N:22]=3)=[CH:19][N:20]=2)[CH2:11][CH2:10][CH2:9][C:8]2[CH:7]=[C:6]([C:12]([O:14]C)=[O:13])[CH:5]=[CH:4][C:3]1=2.[OH-:39].[K+].C1C[O:44]CC1>CO.CS(C)=O>[F:36][C:35]([F:38])([F:37])[C:33]([OH:44])=[O:39].[OH:1][C:2]1([C:16]2[S:17][C:18]([C:21]3[CH:26]=[C:25]([CH3:27])[CH:24]=[C:23]([NH:28][C:29]4[CH:34]=[C:33]([C:35]([F:36])([F:38])[F:37])[CH:32]=[CH:31][N:30]=4)[N:22]=3)=[CH:19][N:20]=2)[CH2:11][CH2:10][CH2:9][C:8]2[CH:7]=[C:6]([C:12]([OH:14])=[O:13])[CH:5]=[CH:4][C:3]1=2

Participants

6

Reactant 3

HCID 8028TetrahydrofuranHCID 14797Potassium HydroxideHCID 70977892(Rac)-methyl 5-hydroxy-5-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5,6,7,8-tetrahydronaphthalene-2-carboxylate

Product 1

HCID 131731736(Rac)-5-hydroxy-5-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid, trifluoroacetate saltYield 45%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 887MethanolSolvent

Procedure

To a solution of (rac)-methyl 5-hydroxy-5-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5,6,7,8-tetrahydronaphthalene-2-carboxylate (250 mg, 0.462 mmol) in THF (1.9 mL) was added potassium hydroxide (40% solution in water, 1.3 mL, 9.25 mmol), and the reaction was stirred at rt for three days. The reaction was diluted with methanol (2 mL) and DMSO (2 mL), barrier filtered, and purified via reverse-phase HPLC (C18 column, water-acetonitrile, TFA modifier) to yield (rac)-5-hydroxy-5-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid, trifluoroacetate salt as a light brown solid (133.8 mg, 0.209 mmol, 45% yield). MS ESI calcd for C26H21F3N4O3S [M+H]+ 527, found 527. 1H NMR (500 MHz, DMSO) δ 10.21 (s, 1H), 8.63 (s, 1H), 8.48 (d, J=5.1 Hz, 1H), 8.23 (s, 1H), 7.72 (s, 1H), 7.66 (d, J=8.0 Hz, 1H), 7.36 (s, 1H), 7.33 (d, J=8.2 Hz, 1H), 7.21 (d, J=5.1 Hz, 1H), 7.10 (s, 1H), 2.92-2.83 (m, 2H), 2.41-2.33 (m, 1H), 2.31 (s, 3H), 2.16-2.07 (m, 1H), 2.04-1.90 (m, 2H) ppm.

Workup

  1. filtrationfiltered
  2. custompurified via reverse-phase HPLC (C18 column, water-acetonitrile, TFA modifier)

Sources & evidence

ORD record
ord-3b284a95dd7a49a49e29b3cb91a72b76
Source dataset
uspto-grants-2014_08
Patent number
US08796310B2

Reaction notes

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