Reaction #1810837

Reaction equation

Chlorosulphonic acid

2-anilino-4-(1-cyclobutyl-2-methylimidazol-5-yl)pyrimidine

HCl

cyclopropylmethylamine

→

title compound

Yield 73.5%

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

Yield 73.5%

Solvents

thionyl chloride

ether

ether

MeOH

Conditions

Workup

1. 1
   Temperaturethen heated at 90° C. for 90 minutes
2. 2
   OtherThe volatiles were removed by evaporation
3. 3
   Otherthe residue was dried under high vacuum (<2 mmHg) for 1 hour
4. 4
   workup.STIRRINGThe mixture was stirred for 30 minutes
5. 5
   Otherthe volatiles were evaporated in vacuo
6. 6
   workup.ADDITIONWater (20 ml) was added
7. 7
   Filtrationthe precipitated solid was collected by filtration
8. 8
   Washwashed with water (2×10 ml)
9. 9
   workup.DISSOLUTIONThe solid was dissolved in MeOH
10. 10
    workup.ADDITIONpoured onto an Isolute amine column
11. 11
    Washeluted first with MeOH (30 ml)
12. 12
    OtherThe solvent was evaporated in vacuo
13. 13
    Otherthe resultant foam triturated with ether
14. 14
    FiltrationThe solid was collected by filtration
15. 15
    Washwashed with ether (2×10 ml)
16. 16
    Otherdried under vacuum at 60° C.
17. 17
    Otherto yield a beige solid
18. 18
    OtherThe resultant solid was triturated with ether
19. 19
    Filtrationcollected by filtration
20. 20
    Otherdried in vacuo

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.

Source