Acetic Acid → HCID 16225381, 화합물

To a reaction vessel charged with 1-methyl-1H-pyrazole-4-carboxaldehyde (84.5 mg, 0.77 mmol) was added a solution of tert-butyl 2-[(4-piperidin-4-ylbenzoyl)amino]phenylcarbamate (prepared as described in Method 1 below; 300 mg, 0.76 mmol) in dichloromethane (7 ml) and N,N-dimethylformamide (0.5 ml). tert-Butyl 2-[(4-piperidin-4-ylbenzoyl)amino]phenylcarbamate may also be prepared according to the process described in Method 4 below. Acetic acid (50 μl, 0.87 mmol) was added and the reaction mixture allowed to stir at ambient temperature for 45 minutes. Sodium triacetoxyborohydride (250 mg, 1.18 mmol) was then added and reactions allowed to stir for a further 76 hours, before being diluted with methanol and poured directly onto an SCX-2 cartridge (10 g). The cartridge was washed through with methanol (80 ml) before eluting the products with a 2M solution of ammonia in methanol (50 ml). The relevant fractions were evaporated to dryness and the resultant residue redissolved in dichloromethane (3 ml) and treated with trifluoroacetic acid (1 ml). This mixture was stirred at ambient temperature for 2 hours before diluting with dichloromethane and pouring onto an SCX-2 cartridge (5 g). The cartridge was washed with methanol (20 ml) then products eluted with a 2M solution of ammonia in methanol (20 ml). The ammoniacal fraction was evaporated to dryness and the resultant residue was purified by flash chromatography on silica, eluting with 10% methanol in dichloromethane, to afford the title compound (117 mg, 40%); NMR Spectrum: (DMSO d6) δ 1.70 (m, 4H), 2.01 (t, 2H), 2.57 (m, 1H), 2.95 (m, 2H), 3.38 (s, 2H), 3.81 (s, 3H), 4.86 (s, 2H), 6.60 (m, 1H), 6.78 (m, 1H), 6.97 (m, 1H), 7.18 (m, 1H), 7.31 (s, 1H), 7.37 (d, 2H), 7.57 (s, 1H), 7.91 (d, 2H), 9.56 (s, 1H); Mass Spectrum: M+H+390.

1. stirringto stir for a further 76 hours
2. additionpoured directly onto an SCX-2 cartridge (10 g)
3. washThe cartridge was washed through with methanol (80 ml)
4. washbefore eluting the products with a 2M solution of ammonia in methanol (50 ml)
5. customThe relevant fractions were evaporated to dryness
6. dissolutionthe resultant residue redissolved in dichloromethane (3 ml)
7. additiontreated with trifluoroacetic acid (1 ml)
8. stirringThis mixture was stirred at ambient temperature for 2 hours
9. additionbefore diluting with dichloromethane
10. additionpouring onto an SCX-2 cartridge (5 g)
11. washThe cartridge was washed with methanol (20 ml)
12. washproducts eluted with a 2M solution of ammonia in methanol (20 ml)
13. customThe ammoniacal fraction was evaporated to dryness
14. customthe resultant residue was purified by flash chromatography on silica
15. washeluting with 10% methanol in dichloromethane

ORD 기록

ord-f8931795691e431292a1f80539482952

출처 데이터셋

uspto-grants-2012_06

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08207202B2