Sulfamide → N-{3-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]oxetan-3-yl}sulfuric diamide

HRID 410582Notes

Reaction equation

HRID 410582 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][O:4][CH2:3]1.[S:29](N)([NH2:32])(=[O:31])=[O:30]>O1CCOCC1.C(OCC)(=O)C>[CH3:17][C:15]1[CH:16]=[C:11]([C:8]2[S:7][C:6]([C:2]3([NH:1][S:29](=[O:31])(=[O:30])[NH2:32])[CH2:3][O: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:28])([F:27])[F:26])[CH:22]=[CH:21][N:20]=2)[CH:14]=1

Participants

5

Reactant 2

HCID 82267SulfamideHCID 58456097N-{3-[2-(3-aminooxetan-3-yl)-1,3-thiazol-5-yl]-5-methylphenyl}-4-(trifluoromethyl)pyrimidin-2-amine

Product 1

HCID 58456182N-{3-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]oxetan-3-yl}sulfuric diamideYield 55.7%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of N-{3-[2-(3-aminooxetan-3-yl)-1,3-thiazol-5-yl]-5-methylphenyl}-4-(trifluoromethyl)pyrimidin-2-amine (Example 59, 25 mg, 0.061 mmol) in dioxane (600 uL), sulfamide (70 mg, 0.725 mmol) was added. The reaction mixture was stirred at 100° C. The resulting mixture was stirred at 100° C. for 4 days. The mixture was diluted with ethyl acetate, washed with saturated aqueous NaHCO3, followed by brine, dried (Na2SO4), filtered and concentrated. The residue was purified by column chromatography on silica (10-100% ethyl acetate in hexanes) and lyophilized to afford N-{3-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]oxetan-3-yl}sulfuric diamide (16.3 mg, 0.034 mmol, 54.6% yield) as a pale yellow solid. MS ESI: [M H]+ m/z 487.0. 1H NMR (500 MHz, DMSO-d6) δ 10.27 (s, 2H), 8.85 (m, 1H), 8.30 (s, 1H), 8.04 (s, 1H), 7.95 (s, 1H), 7.51 (s, 1H), 7.28 (m, 1H), 7.17 (s, 1H), 6.98 (s, 2H), 5.02 (m, 2H), 4.84 (m, 2H), 2.32 (s, 3H). rhSYK activity=+++

Workup

  1. stirringThe resulting mixture was stirred at 100° C. for 4 days
  2. washwashed with saturated aqueous NaHCO3
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by column chromatography on silica (10-100% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-6fbe69d7878341b89ecaaa5405e7540d
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

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