2-Aminopyridine → 2,4-Disubstituted Pyrimidine 4a

HRID 968249Notes

Reaction equation

HRID 968249 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.[H-].[Na+].CS([C:14]1[N:19]=[C:18]([N:20]2[CH:24]=[CH:23][N:22]=[C:21]2[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH:17]=[CH:16][N:15]=1)(=O)=O>C1COCC1>[C:25]1([C:21]2[N:20]([C:18]3[CH:17]=[CH:16][N:15]=[C:14]([NH:1][C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=4)[N:19]=3)[CH:24]=[CH:23][N:22]=2)[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1

Participants

5

Reactant 3

HCID 104392-AminopyridineHCID 24758Sodium hydrideHCID 22288411HCID 22288411, compound

Product 1

HCID 53294302,4-Disubstituted Pyrimidine 4a

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-aminopyridine (31 mg, 0.33 mmol) in dry THF (0.5 mL) was added NaH (32 mg, 1.33 mmol) at room temperature. Once the resulting bubbling had ceased, 2-(methylsulfonyl)-4-(2-phenyl-1H-imidazol-1-yl)pyrimidine (0.100 g, 0.33 mmol) was added all at once. After 1.5 hours the mixture was concentrated in vacuo, diluted with water and the pH of the resulting solution was adjusted to 7 with 1M HCl (aq). The resulting precipitate was filtered and purified by reverse phase HPLC (5-100% CH3CN/H2O+0.1% TFA). 1H-NMR (300 MHz, CDCl3) δ 8.44 (d overlapping with s, J=5.4 Hz, 2H), 8.33 (d, J=4.1 Hz, 1H), 7.93 (d, J=8.3 Hz, 1H), 7.55 (m, 4H), 7.40 (m, 3H), 7.33 (m, 1H), 6.95 (dd, J=4.9, 7.1 Hz, 1H), 6.45 (d, J=5.3 Hz, 1H).

Workup

  1. customOnce the resulting bubbling
  2. concentrationAfter 1.5 hours the mixture was concentrated in vacuo
  3. additiondiluted with water
  4. filtrationThe resulting precipitate was filtered
  5. custompurified by reverse phase HPLC (5-100% CH3CN/H2O+0.1% TFA)

Sources & evidence

ORD record
ord-2b6dfdd04cfb4d87a3148b9da5e0c9ba
Source dataset
uspto-grants-2005_10
Patent number
US06958340B2

Reaction notes

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