Chlorosuccinimide → 2-Amino-5-chloro-4-(1-isopropyl-2-methyl-1H-imidazol-5-yl)pyrimidine

HRID 1441344Notes

Reaction equation

HRID 1441344 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([C:8]2[N:12]([CH:13]([CH3:15])[CH3:14])[C:11]([CH3:16])=[N:10][CH:9]=2)[CH:5]=[CH:4][N:3]=1.[Cl:17]N1C(=O)CCC1=O>C(O)(=O)C>[NH2:1][C:2]1[N:7]=[C:6]([C:8]2[N:12]([CH:13]([CH3:14])[CH3:15])[C:11]([CH3:16])=[N:10][CH:9]=2)[C:5]([Cl:17])=[CH:4][N:3]=1

Participants

4

Reactant 2

HCID 31398ChlorosuccinimideHCID 25178483HCID 25178483, compound

Product 1

HCID 684431582-Amino-5-chloro-4-(1-isopropyl-2-methyl-1H-imidazol-5-yl)pyrimidine

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A solution of 2-amino-4-(1-isopropyl-2-methyl-1H-imidazol-5-yl)pyrimidine (Method 39 of WO 03/076436; 0.5 g, 2.3 mmol) and N-chlorosuccinimide (0.4 g, 3 mmol) in acetic acid (5 ml) was stirred at 65° C. under nitrogen for 2 hours. Then the reaction mixture was allowed to cool down to room temperature and the solvent was removed under vacuum. The crude was taken up in EtOAc and water then portions of solid potassium carbonate were added to this stirred biphasic solution until pH 8-9 was reached. The two layers were separated, the aqueous layer was extracted once with EtOAc then the organics were combined, washed with brine and dried. Removal of the solvent left a residue, which was purified on silica (MeOH/DCM/EtOAc, from 0/50/50 to 6/47/47). Triturating the foam in ether gave a white solid, which was filtered off. (0.49 g, 85%). NMR (CDCl3): 1.51 (d, 6H), 2.55 (s, 3H), 4.85 (septuplet, 1H), 5.01 (b s, 2H), 7.48 (s, 1H), 8.31 (s, 1H); m/z 252 (35Cl), 254 (37Cl); m/z 250 (35Cl), 252 (37Cl).

Workup

  1. customthe solvent was removed under vacuum
  2. additionwater then portions of solid potassium carbonate were added to this stirred biphasic solution until pH 8-9
  3. customThe two layers were separated
  4. extractionthe aqueous layer was extracted once with EtOAc
  5. washwashed with brine
  6. customdried
  7. customRemoval of the solvent
  8. waitleft a residue, which
  9. customwas purified on silica (MeOH/DCM/EtOAc, from 0/50/50 to 6/47/47)
  10. customTriturating the foam in ether
  11. customgave a white solid, which
  12. filtrationwas filtered off

Sources & evidence

ORD record
ord-09348d2347d8413d9e72e248bd715248
Source dataset
uspto-grants-2010_02
Patent number
US07655652B2

Reaction notes

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