Acetic Acid → HCID 58456124, compound

HRID 410586Notes

Reaction equation

Cl[C:2]1[N:7]=[C:6]([C:8]([OH:10])=[O:9])[CH:5]=[CH:4][N:3]=1.[NH2:11][C:12]1[CH:13]=[C:14]([C:19]2[S:23][C:22]([C:24]([OH:30])([CH3:29])[C:25]([F:28])([F:27])[F:26])=[N:21][CH:20]=2)[CH:15]=[C:16]([CH3:18])[CH:17]=1.C(O)(=O)C>O1CCOCC1>[CH3:18][C:16]1[CH:17]=[C:12]([NH:11][C:2]2[N:7]=[C:6]([C:8]([OH:10])=[O:9])[CH:5]=[CH:4][N:3]=2)[CH:13]=[C:14]([C:19]2[S:23][C:22]([C:24]([OH:30])([CH3:29])[C:25]([F:28])([F:27])[F:26])=[N:21][CH:20]=2)[CH:15]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To 2-chloropyrimidine-4-carboxylic acid (175 mg, 1.104 mmol) in dioxane (2.201 mL) was added 2-[5-(3-amino-5-methylphenyl)-1,3-thiazol-2-yl]-1,1,1-trifluoropropan-2-ol (INTERMEDIATE 17, (334 mg, 1.104 mmol) and acetic acid (69.5 μL, 1.214 mmol). The reaction was heated to 100° C. overnight and was complete by LCMS analysis. The reaction was cooled to room temperature and the solvent was removed under reduced pressure. Remaining acetic acid was azeotroped with toluene (2×5 mL) to yield 2-({3-methyl-5-[2-(1,1,1-trifluoro-2-hydroxypropan-2-yl)-1,3-thiazol-5-yl]phenyl}amino)pyrimidine-4-carboxylic acid as a tan powder. MS ESI: [M+H]+ m/z 425.1. 1H NMR (500 MHz, dmso) δ 13.79-13.63 (m, 10.05 (s, 1H), 8.73 (d, J=5.0, 1H), 8.22-8.14 (m, 1H), 8.10 (s, 1H), 7.65 (s, 1H), 7.56 (s, 1H), 7.32 (d, J=5.0, 1H), 7.12 (s, 1H), 2.31 (s, 3H), 1.76 (s, 3H). rhSYK activity=+

Workup

temperatureThe reaction was cooled to room temperature
customthe solvent was removed under reduced pressure
customRemaining acetic acid was azeotroped with toluene (2×5 mL)

Sources & evidence

ORD record: ord-02ab4e78bc664ba1b9d348c0b47a22d5
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08759366B2

Reaction notes

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