HCID 59164499, compound → HCID 59164454, compound

HRID 906567Notes

Reaction equation

HRID 906567 reaction equation
C([N:4]([S:26]([CH3:29])(=[O:28])=[O:27])[N:5]1[C:14](=[O:15])[C:13]2[C:8](=[CH:9][C:10]([C:21]([F:24])([F:23])[F:22])=[C:11]([CH2:16][NH:17]C(=O)C)[CH:12]=2)[NH:7][C:6]1=[O:25])(=O)C>Cl>[NH2:17][CH2:16][C:11]1[CH:12]=[C:13]2[C:8](=[CH:9][C:10]=1[C:21]([F:23])([F:24])[F:22])[NH:7][C:6](=[O:25])[N:5]([NH:4][S:26]([CH3:29])(=[O:27])=[O:28])[C:14]2=[O:15]

Participants

3

Reactant 1

HCID 59164499HCID 59164499, compound

Product 1

HCID 59164454HCID 59164454, compoundYield 77%

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent2×

Procedure

A solution of N-[3-(acetyl-methanesulfonyl-amino)-2,4-dioxo-7-trifluoromethyl-1,2,3,4-tetrahydro-quinazolin-6-ylmethyl]-acetamide (1.8 g, 4.13 mmol) in 2M aq HCl (5.2 mL) was stirred at 80° C. for 2 d. 2M hydrochloric acid (1 mL) was added every half day. Subsequently the solvent was evaporated and the light yellow residue was purified by ion-exchange resin (DOWEX 50*2-100, MeOH): the crude product was dissolved in MeOH, and mixed with a suspension of DOWEX in MeOH and the mixture was stirred at r.t. for 2 h. The resin was then filtered and washed with MeOH (this MeOH fraction was discarded). The resin was suspended in a solution of ammonia in MeOH (7M, 300 mL), stirred for 2 h, filtered and the filtrate was collected. The resin was treated two more times with a solution of ammonia in MeOH as described above and the filtrates were collected. The combined solvent fractions were evaporated to give N-(6-aminomethyl-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl)-methanesulfonamide (1.12 g, 3.18 mmol, 77%) as a yellow solid, 1H-NMR (DMSO-d6, 400 MHz) 3.14 ppm (s, 3H, SO2—CH3); LC-MS rt=0.523 mn; MS: m/z 352.9 [M+H]+ Column: SunFireC18, 4.6*50 mn, 3.5 um; Positive MS Water/Acetonitrile 95:5 to 5:95 in 5 min, Flow: 1.5 mL/min

Workup

  1. customSubsequently the solvent was evaporated
  2. customthe light yellow residue was purified by ion-exchange resin (DOWEX 50*2-100, MeOH)
  3. dissolutionthe crude product was dissolved in MeOH
  4. additionmixed with a suspension of DOWEX in MeOH
  5. filtrationThe resin was then filtered
  6. washwashed with MeOH (this MeOH fraction
  7. stirringstirred for 2 h
  8. filtrationfiltered
  9. customthe filtrate was collected
  10. additionThe resin was treated two more times with a solution of ammonia in MeOH
  11. customwere collected
  12. customThe combined solvent fractions were evaporated

Sources & evidence

ORD record
ord-50a60d5a38334def87296e64dc2fedeb
Source dataset
uspto-grants-2011_09
Patent number
US08012988B2

Reaction notes

Loading…