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

HRID 403045

Reaction equation

HRID 403045 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 stirred 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-e2884078bb1e41baa59ef7bdf317b1ac
Source dataset
uspto-grants-2014_06
Patent number
US08742124B2

Linked notes

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