Acetic Acid → HCID 58456260, compound

HRID 410583Notes

Reaction equation

HRID 410583 reaction equation
[NH2:1][C:2]1([C:6]2[S:7][C:8]([C:11]3[CH:12]=[C:13]([NH:18][C:19]4[N:24]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:22]=[CH:21][N:20]=4)[CH:14]=[C:15]([CH3:17])[CH:16]=3)=[CH:9][N:10]=2)[CH2:5][CH2:4][CH2:3]1.C(O)(=O)C.[O-:33][C:34]#[N:35].[K+]>C1COCC1.O>[CH3:17][C:15]1[CH:16]=[C:11]([C:8]2[S:7][C:6]([C:2]3([NH:1][C:34]([NH2:35])=[O:33])[CH2:3][CH2:4][CH2:5]3)=[N:10][CH:9]=2)[CH:12]=[C:13]([NH:18][C:19]2[N:24]=[C:23]([C:25]([F:27])([F:28])[F:26])[CH:22]=[CH:21][N:20]=2)[CH:14]=1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 11378442Potassium cyanateHCID 67257371HCID 67257371, compound

Product 1

HCID 58456260HCID 58456260, compoundYield 55.3%

Reagents, catalysts & solvents 1

HCID 21881883Oxolane--water (1/1)Solvent

Procedure

To a solution of N-{3-[2-(1-aminocyclobutyl)-1,3-thiazol-5-yl]-5-methylphenyl}-4-(trifluoromethyl)pyrimidin-2-amine (Example 61B-1, 50 mg, 0.123 mmol) and acetic acid (7 μL, 0.123 mmol) in THF/water (1.6:1, 2.1 mL), potassium cyanate (10 mg, 0.123 mmol) was added. The reaction mixture was stirred overnight at room temperature and then concentrated. The residue was purified by column chromatography on silica (50-100% ethyl acetate in hexanes, 0-20% methanol in dichloromethane) and lyophilized to afford 1-{1-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]cyclobutyl}urea (31.3 mg, 0.068 mmol, 54.9%) as a white powder. MS ESI: [M+H]+ m/z 449.1. 1H NMR (500 MHz, DMSO-d6 δ 10.23 (s, 1H), 8.82 (d, J=4.9, 1H), 7.93 (s, 1H), 7.90 (s, 1H), 7.47 (s, 1H), 7.27 (d, J=4.9, 1H), 7.15-7.00 (m, 2H), 5.58 (s, 2H), 2.63-2.51 (m, 2H), 2.32 (m, 5H), 1.96 (m, 2H). rhSYK activity=+++

Workup

  1. concentrationconcentrated
  2. customThe residue was purified by column chromatography on silica (50-100% ethyl acetate in hexanes, 0-20% methanol in dichloromethane)

Sources & evidence

ORD record
ord-015e72a0872c414ca28a043fe94d6c16
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

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