Lithium Hexamethyldisilazide → N-{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}-2-(1,3-thiazol-4-ylmethoxy)pyrimidine-5-carboxamide

HRID 550071

Reaction equation

HRID 550071 reaction equation
[S:1]1[CH:5]=[C:4]([CH2:6][OH:7])[N:3]=[CH:2]1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH:18]1([NH:21][C:22]([C:24]2[CH:25]=[CH:26][C:27]([CH3:43])=[C:28]([NH:30][C:31]([C:33]3[CH:34]=[N:35][C:36](S(C)(=O)=O)=[N:37][CH:38]=3)=[O:32])[CH:29]=2)=[O:23])[CH2:20][CH2:19]1>C1COCC1>[CH:18]1([NH:21][C:22]([C:24]2[CH:25]=[CH:26][C:27]([CH3:43])=[C:28]([NH:30][C:31]([C:33]3[CH:34]=[N:35][C:36]([O:7][CH2:6][C:4]4[N:3]=[CH:2][S:1][CH:5]=4)=[N:37][CH:38]=3)=[O:32])[CH:29]=2)=[O:23])[CH2:20][CH2:19]1

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 2763215(1,3-Thiazol-4-yl)methanolHCID 66630813N-{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}-2-(methylsulfonyl)pyrimidine-5-carboxamide

Product 1

HCID 11258351N-{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}-2-(1,3-thiazol-4-ylmethoxy)pyrimidine-5-carboxamideYield 23%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of thiazole-4-methanol (79 mg) in THF (1 mL) at 0° C. under argon was added 1M lithium bis(trimethylsilyl)amide in THF (0.35 mL). After 30 minutes N-{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}-2-(methylsulfonyl)pyrimidine-5-carboxamide (127 mg, 0.34 mmol) in THF (3 mL) was added and the reaction warmed to room temperature and stiired for 5 hours. The reaction mixture was partitioned between ethyl acetate and water, the organic phases washed with brine, dried (Na2SO4) and concentrated. The residue was purified by flash chromatography on a 12 g silica cartridge eluting with a gradient of 0 to 5% Methanol/DCM to give the title compound as a solid (31 mg, 23%); NMR Spectrum: (DMSOd6) 0.56 (m, 2H), 0.69 (m, 2H), 2.29 (s, 3H), 2.85 (m, 1H), 5.63 (s, 2H), 7.36, (d, 1H) 7.67 (dd, 1H), 7.83 (dd, 2H), 8.49 (d, 1H), 9.14 (m, 2H), 10.14 (s, 1H); Mass Spectrum: M+H+ 410.

Workup

  1. customThe reaction mixture was partitioned between ethyl acetate and water
  2. washthe organic phases washed with brine
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated
  5. customThe residue was purified by flash chromatography on a 12 g silica cartridge
  6. washeluting with a gradient of 0 to 5% Methanol/DCM

Sources & evidence

ORD record
ord-d67ba99257894ab39c5a8d32338567ee
Source dataset
uspto-grants-2011_05
Patent number
US07943776B2

Linked notes

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