Piconol → N-{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}-2-(pyridin-2-ylmethoxy)pyrimidine-5-carboxamide

HRID 403042Notes

Reaction equation

HRID 403042 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][OH:8].C[Si](C)(C)[N-][Si](C)(C)C.[Li+].[CH:19]1([NH:22][C:23]([C:25]2[CH:26]=[CH:27][C:28]([CH3:44])=[C:29]([NH:31][C:32]([C:34]3[CH:35]=[N:36][C:37](S(C)(=O)=O)=[N:38][CH:39]=3)=[O:33])[CH:30]=2)=[O:24])[CH2:21][CH2:20]1>C1COCC1>[CH:19]1([NH:22][C:23]([C:25]2[CH:26]=[CH:27][C:28]([CH3:44])=[C:29]([NH:31][C:32]([C:34]3[CH:35]=[N:36][C:37]([O:8][CH2:7][C:2]4[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=4)=[N:38][CH:39]=3)=[O:33])[CH:30]=2)=[O:24])[CH2:21][CH2:20]1

Participants

5

Reactant 3

HCID 11474PiconolHCID 2733832Lithium HexamethyldisilazideHCID 66630813N-{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}-2-(methylsulfonyl)pyrimidine-5-carboxamide

Product 1

HCID 11475163N-{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}-2-(pyridin-2-ylmethoxy)pyrimidine-5-carboxamideYield 12.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 2-pyridinylmethanol (258 μl, 2.67 mmol) in THF (50 mL) cooled in ice bath to 0° C. was added dropwise lithium hexamethyldisilazide (1M solution in THF, 2.67 mL, 2.67 mmol) and the resulting mixture stirred for 30 minutes at 0° C. N-{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}-2-(methylsulfonyl)pyrimidine-5-carboxamide (1 g, 2.67 mmol) was added and the resulting mixture stirred for 16 h at room temperature. The reaction mixture was concentrated under reduced pressure and the residue partitioned between water and DCM. Concentration of the organic phase under reduced pressure and crystallisation from acetonitrile gave the title compound as a colourless solid (132 mg, 12%); NMR Spectrum: (DMSOd6) 0.57 (m, 2H), 0.69 (m, 2H), 2.30 (s, 3H), 2.86 (m, 1H), 5.61 (s, 2H), 7.36 (m, 2H), 7.49 (m, 1H), 7.66 (m, 1H), 7.85 (m, 2H), 8.38 (m, 1H), 8.58 (m, 1H), 9.16 (s, 2H), 10.16 (s, 1H); Mass Spectrum: M+H+ 404.

Workup

  1. stirringthe resulting mixture stirred for 16 h at room temperature
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. customthe residue partitioned between water and DCM
  4. customConcentration of the organic phase under reduced pressure and crystallisation from acetonitrile

Sources & evidence

ORD record
ord-1f12a8bcccca414fa0f39903d4fd9aec
Source dataset
uspto-grants-2014_06
Patent number
US08742124B2

Reaction notes

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