Hydrochloric Acid → 4-(1-Cyclobutyl-2-methylimidazol-5-yl)-2-{4-[N-(cycloproylmethyl)sulphamoyl]anilino}pyrimidine

HRID 1723655Notes

Reaction equation

HRID 1723655 reaction equation
Cl[S:2]([OH:5])(=O)=[O:3].[NH:6]([C:13]1[N:18]=[C:17]([C:19]2[N:23]([CH:24]3[CH2:27][CH2:26][CH2:25]3)[C:22]([CH3:28])=[N:21][CH:20]=2)[CH:16]=[CH:15][N:14]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[CH:29]1([CH2:32][NH2:33])[CH2:31][CH2:30]1.Cl>S(Cl)(Cl)=O.CO.CCOCC>[CH:24]1([N:23]2[C:19]([C:17]3[CH:16]=[CH:15][N:14]=[C:13]([NH:6][C:7]4[CH:8]=[CH:9][C:10]([S:2](=[O:5])(=[O:3])[NH:33][CH2:32][CH:29]5[CH2:31][CH2:30]5)=[CH:11][CH:12]=4)[N:18]=3)=[CH:20][N:21]=[C:22]2[CH3:28])[CH2:27][CH2:26][CH2:25]1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 24638Chlorosulfonic acidHCID 75646CyclopropanemethanamineHCID 688838442-Anilino-4-(1-cyclobutyl-2-methylimidazol-5-yl)pyrimidine

Product 1

HCID 689791654-(1-Cyclobutyl-2-methylimidazol-5-yl)-2-{4-[N-(cycloproylmethyl)sulphamoyl]anilino}pyrimidineYield 73.5%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 3283Diethyl EtherSolvent2×HCID 24386Thionyl ChlorideSolvent

Conditions

Temperature
0 °C

Procedure

Chlorosulphonic acid (150 μl, 2.16 mmol) was added dropwise to solution of 2-anilino-4-(1-cyclobutyl-2-methylimidazol-5-yl)pyrimidine (Method 61; 165 mg, 0.54 mmol) in thionyl chloride (3 ml), cooled to 0° C. and the mixture stirred at 0° C. for 10 minutes then heated at 90° C. for 90 minutes. The volatiles were removed by evaporation and the residue was dried under high vacuum (<2 mmHg) for 1 hour. The resulting solid was placed under nitrogen and a solution of cyclopropylmethylamine (700 μl, 8.1 mmol) in MeOH (3 ml) added. The mixture was stirred for 30 minutes and the volatiles were evaporated in vacuo. Water (20 ml) was added and the precipitated solid was collected by filtration, washed with water (2×10 ml). The solid was dissolved in MeOH and poured onto an Isolute amine column and eluted first with MeOH (30 ml). The solvent was evaporated in vacuo and the resultant foam triturated with ether. The solid was collected by filtration and washed with ether (2×10 ml) and dried under vacuum at 60° C. to yield a beige solid. The solid was slurried in ether (6 ml), 1M HCl in ether (2 ml, 2 mmol) and the solvent evaporated in vacuo. The resultant solid was triturated with ether, collected by filtration and dried in vacuo to yield the title compound (174 mg, 63%) as a hygroscopic solid. NMR: 0.05 (m, 2H), 0.34 (m, 2H), 0.79 (m, 1H), 1.70 (m, 2H), 2.37 (m, 4H), 2.62 (m, 2H), 2.75 (s, 3H), 5.40 (m, 1H), 7.23 (d, 1H), 7.54 (brs, 1H), 7.76 (d, 2H), 7.91 (d, 2H), 8.14 (s, 1H), 8.68 (d, 1H), 10.26 (brs, 1H); m/z 429.

Workup

  1. temperaturethen heated at 90° C. for 90 minutes
  2. customThe volatiles were removed by evaporation
  3. customthe residue was dried under high vacuum (<2 mmHg) for 1 hour
  4. stirringThe mixture was stirred for 30 minutes
  5. customthe volatiles were evaporated in vacuo
  6. additionWater (20 ml) was added
  7. filtrationthe precipitated solid was collected by filtration
  8. washwashed with water (2×10 ml)
  9. dissolutionThe solid was dissolved in MeOH
  10. additionpoured onto an Isolute amine column
  11. washeluted first with MeOH (30 ml)
  12. customThe solvent was evaporated in vacuo
  13. customthe resultant foam triturated with ether
  14. filtrationThe solid was collected by filtration
  15. washwashed with ether (2×10 ml)
  16. customdried under vacuum at 60° C.
  17. customto yield a beige solid
  18. customThe resultant solid was triturated with ether
  19. filtrationcollected by filtration
  20. customdried in vacuo

Sources & evidence

ORD record
ord-910a7075d1e547f78d5b5f1899299538
Source dataset
uspto-grants-2009_02
Patent number
US07485638B2

Reaction notes

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