Cyanogen Bromide → 6-{[6-(4-fluorophenyl)[1,2,4]triazolo[4,3-b]pyridazin-3-yl]sulphanyl}-1H-benzimidazol-2-amine

HRID 633479Notes

Reaction equation

HRID 633479 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[CH:10][C:11]3[N:12]([C:14]([S:17][C:18]4[CH:19]=[C:20]([NH2:25])[C:21]([NH2:24])=[CH:22][CH:23]=4)=[N:15][N:16]=3)[N:13]=2)=[CH:4][CH:3]=1.[N:26]#[C:27]Br.[OH-].[Na+]>C(O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[CH:10][C:11]3[N:12]([C:14]([S:17][C:18]4[CH:23]=[CH:22][C:21]5[N:24]=[C:27]([NH2:26])[NH:25][C:20]=5[CH:19]=4)=[N:15][N:16]=3)[N:13]=2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 10476Cyanogen BromideHCID 14798Sodium HydroxideHCID 675241354-{[6-(4-Fluorophenyl)[1,2,4]triazolo[4,3-b]pyridazin-3-yl]sulphanyl}benzene-1,2-diamine

Product 1

HCID 251828586-{[6-(4-fluorophenyl)[1,2,4]triazolo[4,3-b]pyridazin-3-yl]sulphanyl}-1H-benzimidazol-2-amine

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of 4-{[6-(4-fluorophenyl)[1,2,4]triazolo[4,3-b]pyridazin-3-yl]sulphanyl}benzene-1,2-diamine and of 42 mg of cyanogen bromide in 10 cm3 of ethanol is brought to reflux for 3 hours. The resulting reaction mixture is then run into a 2.5N aqueous solution of sodium hydroxide and the mixture obtained is subsequently extracted with a 90/10 mixture of ethyl acetate and methanol. The organic phases are combined then dried over magnesium sulphate and then evaporated. A yellow powder is recovered, and is chromatographed on Biotage Quad 12/25 (KP-SIL, 60 A; 32-63 μM), elution being carried out with a gradient of dichloromethane and then dichloromethane/eluent B: 95/5, 92.5/7.5, 90/10, 87.5/12.5, 85/15 (eluent B=dichloromethane/methanol/aqueous ammonia 38/17/2). 43.2 mg of 6-{[6-(4-fluorophenyl)[1,2,4]triazolo[4,3-b]pyridazin-3-yl]sulphanyl}-1H-benzimidazol-2-amine are thus obtained in the form of a whitish powder, the characteristics of which are as follows:

Workup

  1. temperatureto reflux for 3 hours
  2. customThe resulting reaction mixture
  3. customthe mixture obtained
  4. extractionis subsequently extracted with a 90/10 mixture of ethyl acetate and methanol
  5. dry with materialThe organic phases are combined then dried over magnesium sulphate
  6. customevaporated
  7. customA yellow powder is recovered
  8. customis chromatographed on Biotage Quad 12/25 (KP-SIL, 60 A
  9. wash32-63 μM), elution

Sources & evidence

ORD record
ord-f1479c4764664e429cef6355fe952016
Source dataset
uspto-grants-2016_04
Patent number
US09321777B2

Reaction notes

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