Hydrochloric Acid → 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

HRID 2402388Notes

Reaction equation

HRID 2402388 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.[Li+].[OH-].Cl>CCO>[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

5

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 86680803(R)-methyl 5-hydroxy-5-(5-(4-methyl-6-(4-(trifluoromethyl)pyridin-2-ylamino)pyridin-2-yl)thiazol-2-yl)-5,6,7,8-tetrahydronaphthalene-2-carboxylate

Product 1

HCID 709779865-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

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
45 °C

Procedure

To a suspension of (R)-methyl 5-hydroxy-5-(5-(4-methyl-6-(4-(trifluoromethyl)pyridin-2-ylamino)pyridin-2-yl)thiazol-2-yl)-5,6,7,8-tetrahydronaphthalene-2-carboxylate (12.8 g, 23.68 mmol) in EtOH (192 mL), was added 1N aqueous LiOH (83 mL, 83 mmol). The white suspension was heated to 45° C. for 4 h, during which time the reaction became bright yellow. The reaction was cooled to rt and acidified with 1N aqueous HCl to pH=4 during which time the product precipitated. Filtration afforded (R) 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 as an off white solid (11.5 g, 92% yield). MS ESI calcd for C26H21F3N4O3S [M+H]+ 527, found 527. 1H NMR (500 MHz, DMSO) δ 12.85 (s, 1H), 10.20 (s, 1H), 8.64 (s, 1H), 8.48 (d, J=5.1 Hz, 1H), 8.23 (s, 1H), 7.72 (s, 1H), 7.66 (d, J=8.1 Hz, 1H), 7.38-7.31 (m, 2H), 7.21 (d, J=4.9 Hz, 1H), 7.10 (s, 1H), 6.60 (s, 1H), 2.92-2.82 (m, 2H), 2.40-2.33 (m, 1H), 2.30 (s, 3H), 2.15-2.08 (m, 1H), 2.03-1.88 (m, 2H) ppm.

Workup

  1. temperatureThe reaction was cooled to rt
  2. customprecipitated
  3. filtrationFiltration

Sources & evidence

ORD record
ord-864f4d51c4e5406db7b407c02e64f48e
Source dataset
uspto-grants-2014_08
Patent number
US08796310B2

Reaction notes

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