Hydrochloric Acid → 5-{1-Hydroxy-1-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]ethyl}pyridine-2-carboxylic acid

HRID 1040190Notes

Reaction equation

HRID 1040190 reaction equation
[OH:1][C:2]([C:27]1[CH:28]=[CH:29][C:30]([C:33]([O:35]C)=[O:34])=[N:31][CH:32]=1)([C:4]1[S:5][C:6]([C:9]2[CH:14]=[C:13]([NH:15][C:16]3[N:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[CH:18][N:17]=3)[CH:12]=[C:11]([CH3:26])[CH:10]=2)=[CH:7][N:8]=1)[CH3:3].[OH-].[Na+].Cl>CO.O>[OH:1][C:2]([C:27]1[CH:28]=[CH:29][C:30]([C:33]([OH:35])=[O:34])=[N:31][CH:32]=1)([C:4]1[S:5][C:6]([C:9]2[CH:14]=[C:13]([NH:15][C:16]3[N:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[CH:18][N:17]=3)[CH:12]=[C:11]([CH3:26])[CH:10]=2)=[CH:7][N:8]=1)[CH3:3]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 67430690Methyl 5-{1-hydroxy-1-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]ethyl}pyridine-2-carboxylate

Product 1

HCID 584561465-{1-Hydroxy-1-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]ethyl}pyridine-2-carboxylic acidYield 92%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

The product of Step 2 (95 mg, 0.184 mmol) was taken up in MeOH (2.0 ml) in a microwave vial, and sodium hydroxide (1.0 M in H2O, 0.369 ml, 0.369 mmol) was added. The reaction was heated to 100° C. for 10 min in the microwave. The colorless solution was adjusted to a pH of 3-4 with 1 N HCl, diluted with water, and extracted with 15% IPA/CHCl3 (2×). The combined organic layers were dried (MgSO4), filtered and evaporated to afford the title compound (85 mg, 0.169 mmol, 92% yield) as an off-white foam. MS ESI: [M+H]+ m/z 502.1. 1H NMR (600 MHz, DMSO-d6) δ 13.12 (s, 1H), 10.23 (s, 1H), 8.89 (d, J=1.9, 1H), 8.80 (d, J=4.9, 1H), 8.09 (dd, J=2.3, 8.2, 1H), 7.99 (d, J=8.2, 1H), 7.97 (s, 1H), 7.92 (s, 1H), 7.44 (s, 1H), 7.25 (d, J=4.9, 1H), 7.13 (d, J=4.5, 2H), 2.28 (s, 3H), 1.95 (s, 3H). rhSYK activity=+++

Workup

  1. additionwas added
  2. extractionextracted with 15% IPA/CHCl3 (2×)
  3. dry with materialThe combined organic layers were dried (MgSO4)
  4. filtrationfiltered
  5. customevaporated

Sources & evidence

ORD record
ord-3d3ca541e74641e081e0f57e6a6c98bc
Source dataset
uspto-grants-2013_10
Patent number
US08551984B2

Reaction notes

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