Sulfamide → HCID 482361, compound

HRID 2393285Notes

Reaction equation

HRID 2393285 reaction equation
[C:1]([C:3]1[CH:12]=[C:11]2[C:6]([C:7](=[O:31])[N:8]([C@H:13]([CH3:30])[C@:14]([C:22]3[CH:27]=[CH:26][C:25]([F:28])=[CH:24][C:23]=3[F:29])([OH:21])[CH2:15][N:16]3[CH:20]=[N:19][CH:18]=[N:17]3)[CH:9]=[N:10]2)=[CH:5][CH:4]=1)#[N:2].S(N)(N)(=O)=[O:33]>CO.C(Cl)(Cl)Cl>[NH2:2][C:1]([C:3]1[CH:12]=[C:11]2[C:6]([C:7](=[O:31])[N:8]([C@H:13]([CH3:30])[C@:14]([C:22]3[CH:27]=[CH:26][C:25]([F:28])=[CH:24][C:23]=3[F:29])([OH:21])[CH2:15][N:16]3[CH:20]=[N:19][CH:18]=[N:17]3)[CH:9]=[N:10]2)=[CH:5][CH:4]=1)=[O:33]

Participants

5

Reactant 2

HCID 82267SulfamideHCID 482347HCID 482347, compound

Product 1

HCID 482361HCID 482361, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6212ChloroformSolvent

Procedure

A solution of (1R,2R)-7-cyano-3-[2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]quinazolin-4(3H)-one (obtained in example 2, 500 mg, 1.2 mmol) in MeOH (5 mL) and CHCl3 (5 mL) was cooled to 0° C. and HCl gas was bubbled until saturation (1.5 h). The mixture was allowed to stand at 0° C. overnight and was then concentrated and the residue was slowly added to aqueous K2CO3 solution (2.5 g). The yellowish precipitate formed was filtered, dried, taken up in methanol and allowed to react with sulfamide (350 mg, 3.6 mmol) at reflux for 3 h. The reaction mixture was then concentrated and partitioned between water and CHCl3. The organic layer was separated, dried over Na2SO4, filtered, concentrated and the resulting residue, whose thin layer chromatography showed the presence of three different compounds, was flash chromatographed. The first compound to elute was identified as the methyl imidate. The second compound to elute was the amide (title compound), the physical parameters of which are as follows: mp 235°-236° C.; 1H NMR (300 MHz, CDCl3) δ (TMS) 8.63 (s, 1H, N=CH--N), 8.42 (d, J=8.2, 1H, arom), 8.13 (d, J=1.5, 1H, arom), 7.98 (dd, J=8.2, J=1.5, 1H, arom), 7.77 (s, 1H, triazole), 7.74 (s, 1H, triazole), 7.48 (dt, Jd =6.4, Jt =8.8, 1H, arom), 6.9-6.8 (m, 2H, arom), 6.3 (broad s, 2H, NH2), 5.92 (dq, Jd =1.2, Jq =7.3, 1H, MeCH), 5.56 (d, J=1.3, 1H, OH), 5.16 (d, J=14.1, 1H, CH(H)), 4.03 (d, J=14.1, 1H, CH(H)), 1.32 (d, J=7.3, 3H, CHMe); GC/MS 224 (Tr--CH2COHAr, C10H8F2N3O), 216 (N-ethylheterocycle-1, C11H11N3O2).

Workup

  1. customHCl gas was bubbled until saturation (1.5 h)
  2. concentrationwas then concentrated
  3. additionthe residue was slowly added to aqueous K2CO3 solution (2.5 g)
  4. customThe yellowish precipitate formed
  5. filtrationwas filtered
  6. customdried
  7. temperatureat reflux for 3 h
  8. concentrationThe reaction mixture was then concentrated
  9. custompartitioned between water and CHCl3
  10. customThe organic layer was separated
  11. dry with materialdried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customchromatographed
  15. washThe first compound to elute
  16. washThe second compound to elute

Sources & evidence

ORD record
ord-40f0efc2575a441aa42106964894e628
Source dataset
uspto-grants-1998_09
Patent number
US05807854

Reaction notes

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