(+/-)-5-(3-chlorophenyl)-alpha-(4-chlorophenyl)-alpha-(1-methyl-1H-imidazol-5-yl)tetrazolo[1,5-a]quinazoline-7-methanol → (4-chlorophenyl)(5-(3-chlorophenyl)tetrazolo[1,5-a]quinazolin-7-yl)(1-methyl-1H-imidazol-5-yl)methanamine

HRID 1879955Notes

Reaction equation

HRID 1879955 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:17]3[C:12](=[CH:13][CH:14]=[C:15]([C:18]([C:26]4[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][CH:27]=4)([C:20]4[N:24]([CH3:25])[CH:23]=[N:22][CH:21]=4)O)[CH:16]=3)[N:11]3[N:33]=[N:34][N:35]=[C:10]3[N:9]=2)[CH:5]=[CH:6][CH:7]=1.S(=[N:39]C(N)=O)(=O)=O>>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:17]3[C:12](=[CH:13][CH:14]=[C:15]([C:18]([C:26]4[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][CH:27]=4)([C:20]4[N:24]([CH3:25])[CH:23]=[N:22][CH:21]=4)[NH2:39])[CH:16]=3)[N:11]3[N:33]=[N:34][N:35]=[C:10]3[N:9]=2)[CH:5]=[CH:6][CH:7]=1

Participants

3

Reactant 2

HCID 9870665(+/-)-5-(3-chlorophenyl)-alpha-(4-chlorophenyl)-alpha-(1-methyl-1H-imidazol-5-yl)tetrazolo[1,5-a]quinazoline-7-methanolHCID 118190831-Sulfonylurea

Product 1

HCID 9848861(4-chlorophenyl)(5-(3-chlorophenyl)tetrazolo[1,5-a]quinazolin-7-yl)(1-methyl-1H-imidazol-5-yl)methanamineYield 26,106.5%

Conditions

Temperature
160 °C

Procedure

A mixture of intermediate (3) (0.0061 mol) and sodium azide (0.0079 mol) in N,N-dimethylacetamide (DMA)(20 ml) was stirred at 50° C. for 18 hours. The mixture was cooled to room temperature and poured out into ice water. The precipitate was filtered off, washed with H2O thoroughly and taken up in CH2Cl2. The organic solution was dried, filtered and the solvent was evaporated. The residue was crystallized from CH3CN DIPE. The precipitate was filtered off and dried yielding 2.3 g (75%) of (±)-5-(3-chlorophenyl)-α-(4-chlorophenyl)-α-(1-methyl-1H-imidazol-5-yl)tetrazolo[1,5-a]quinazoline-7-methanol (intermediate 4); mp. 232-233° C. d) A mixture of intermediate (4) (0.0573 mmol) and sulfonylurea (300 g) was stirred at 160° C. for 5 hours and then cooled. Ice water was added, then methylene chloride and the mixture was filtered over celite. The organic layer was separated, dried (MgSO4), filtered and the solvent was evaporated till dryness. The residue was purified by column chromatography over silica gel. The pure fraction were collected and the solvent was evaporated yielding 7.5 g (26%) of (±)-5-(3-chlorophenyl)-α-(4-chloro-phenyl)-α-(1-methyl-1H-imidazol-5-yl)tetrazolo[1,5-a]quinazoline-7-methanamine (intermediate 5). e) Intermediate (5) was separated into its enantiomers and purified by column chromatography over Chiralpak AD® (eluent: hexane/EtOH 50/50; 15-35 μm). The pure first (A) fractions were collected and the solvent was evaporated yielding 3.3 g of residue which was crystallized from CH3CN/DIPE. The precipitate was filtered off and dried, yielding 2.55 g of (−)-5-(3-chlorophenyl)-α-(4-chlorophenyl)-α-(1-methyl-1H-imidazol-5-yl)tetrazolo[1,5-a]quinazoline-7-methanamine (compound 1)[α]D20=−7.16°(c=5 mg/ml MeOH); mp.=178-180° C.; 1H-NMR (DMSO, 400 MHz) δ in ppm:

Workup

  1. temperaturecooled
  2. filtrationmethylene chloride and the mixture was filtered over celite
  3. customThe organic layer was separated
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customthe solvent was evaporated till dryness
  7. customThe residue was purified by column chromatography over silica gel
  8. customThe pure fraction were collected
  9. customthe solvent was evaporated

Sources & evidence

ORD record
ord-2855dc1a323e472b9045cfc1f740b460
Source dataset
uspto-grants-2012_11
Patent number
US08318753B2

Reaction notes

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