Ammonium Chloride → HCID 178428376, compound

HRID 2305966Notes

Reaction equation

HRID 2305966 reaction equation
[C:1]([NH:3][C:4]1[CH:25]=[C:24]([CH3:26])[C:7]([O:8][C:9]2[CH:10]=[CH:11][C:12]([OH:23])=[C:13]([CH:22]=2)[C:14]([N:16]([CH:18]2[CH2:21][CH2:20][CH2:19]2)[CH3:17])=[O:15])=[C:6]([CH3:27])[CH:5]=1)#[N:2].[N-:28]=[N+:29]=[N-:30].[Na+].[Cl-].[NH4+]>>[CH:18]1([N:16]([CH3:17])[C:14](=[O:15])[C:13]2[CH:22]=[C:9]([O:8][C:7]3[C:6]([CH3:27])=[CH:5][C:4]([NH:3][C:1]4[NH:30][N:29]=[N:28][N:2]=4)=[CH:25][C:24]=3[CH3:26])[CH:10]=[CH:11][C:12]=2[OH:23])[CH2:21][CH2:20][CH2:19]1

Participants

4

Reactant 3

HCID 25517Ammonium ChlorideHCID 33557Sodium AzideHCID 18433420HCID 18433420, compound

Product 1

HCID 178428376HCID 178428376, compound

Conditions

Temperature
165 °C

Procedure

N-Cyclobutyl-5-[2,6-dimethyl-4-(1H-tetrazol-5-ylamino)-phenoxy]-2-hydroxy-N-methyl-benzamide was prepared from 5-(4-cyanoamino-2,6-dimethyl-phenoxy)-N-cyclobutyl-2-hydroxy-N-methyl-benzamide according to a procedure analogous to that described in EXAMPLE 1, Step C. Sodium azide (1.2 equiv) and ammonium chloride (10 equiv) were used, and the reaction was heated to 165° C. for 5 hours. After the reaction had been acidified, the aqueous mixture was washed with ethyl acetate (3×10 ml). The combined organic extracts were extracted with aqueous 1N HCl (3×50 ml), and brine (50 ml). The organic phase was dried over anhydrous Na2SO4, filtered, and concentrated. The residue was purified by preparative TLC (methanol:water:dichloromethane 15:1.5:83.5) to afford the title product of Example 6. MS (APCI+) Calc.: 408.5, Found: 409.2 (M+1).

Workup

  1. washthe aqueous mixture was washed with ethyl acetate (3×10 ml)
  2. extractionThe combined organic extracts were extracted with aqueous 1N HCl (3×50 ml), and brine (50 ml)
  3. dry with materialThe organic phase was dried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by preparative TLC (methanol:water:dichloromethane 15:1.5:83.5)

Sources & evidence

ORD record
ord-a1aa2026a997456981ec01e29eafb209
Source dataset
uspto-grants-2002_08
Patent number
US06441015B2

Reaction notes

Loading…