1,4-Dioxane → N-{3-[2-(3-aminooxetan-3-yl)-1,3-thiazol-5-yl]-5-methylphenyl}-4-(trifluoromethyl)pyrimidin-2-amine

HRID 410576Notes

Reaction equation

HRID 410576 reaction equation
CC(S([NH:7][C:8]1([C:12]2[S:13][C:14]([C:17]3[CH:22]=[C:21]([NH:23][C:24]4[N:29]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:27]=[CH:26][N:25]=4)[CH:20]=[C:19]([CH3:34])[CH:18]=3)=[CH:15][N:16]=2)[CH2:11][O:10][CH2:9]1)=O)(C)C.O1CCOCC1>CO.Cl.C(OCC)(=O)C>[NH2:7][C:8]1([C:12]2[S:13][C:14]([C:17]3[CH:22]=[C:21]([NH:23][C:24]4[N:29]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:27]=[CH:26][N:25]=4)[CH:20]=[C:19]([CH3:34])[CH:18]=3)=[CH:15][N:16]=2)[CH2:9][O:10][CH2:11]1

Participants

6

Reactant 2

HCID 312751,4-DioxaneHCID 672573262-methyl-N-{3-[5-(3-methyl-5-[[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]oxetan-3-yl]propane-2-sulfinamide

Product 1

HCID 58456097N-{3-[2-(3-aminooxetan-3-yl)-1,3-thiazol-5-yl]-5-methylphenyl}-4-(trifluoromethyl)pyrimidin-2-amineYield 53.5%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution the product of Step 2 (1.01 g, 1.964 mmol) in methanol (9.8 mL), 4M HCl in Dioxane (1.97 mL, 7.86 mmol) was added. The mixture was stirred at room temperature for 15 minutes. The mixture was diluted with ethyl acetate, washed with saturated NaHCO3, followed by brine, dried (Na2SO4), filtered and concentrated. The residue was purified by column chromatography on silica (40-100% ethyl acetate in hexanes) to afford N-{3-[2-(3-aminooxetan-3-yl)-1,3-thiazol-5-yl]-5-methylphenyl}-4-(trifluoromethyl)pyrimidin-2-amine (386.6 mg, 0.954 mmol, 53.5% yield) as a pale yellow solid. MS ESI: [M+H]+ m/z 408.0. 1H NMR (500 MHz, DMSO-d6) δ 10.26 (s, 1H), 8.83 (d, J=4.8, 1H), 8.07 (s, 1H), 7.97 (s, 1H), 7.47 (s, 1H), 7.28 (d, J=4.9, 1H), 7.17 (s, 1H), 4.87 (d, J=5.6, 2H), 4.58 (d, J=5.7, 2H), 2.32 (s, 3H).

Workup

  1. washwashed with saturated NaHCO3
  2. dry with materialdried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified by column chromatography on silica (40-100% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-bad4cb84b5b84cc28bbcd786525dc8f4
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

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