Thionyl Chloride → 6-[5-(6-chloropyridin-3-yl)-1,2,4-oxadiazol-3-yl]-2-N-methyl-2-N-phenyl-1,3,5-triazine-2,4-diamine

HRID 341497Notes

Reaction equation

HRID 341497 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][C:5]([C:8]([OH:10])=O)=[CH:4][CH:3]=1.S(Cl)(Cl)=O.[NH2:15][C:16]1[N:21]=[C:20]([N:22]([CH3:29])[C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[N:19]=[C:18]([C:30](=[NH:33])[NH:31]O)[N:17]=1.NC1N=C(N(C)C2C=CC=C(C)C=2)N=C(C(NO)=N)N=1>N1C=CC=CC=1>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[O:10][N:33]=[C:30]([C:18]3[N:19]=[C:20]([N:22]([CH3:29])[C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)[N:21]=[C:16]([NH2:15])[N:17]=3)[N:31]=2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 24386Thionyl ChlorideHCID 792226-Chloronicotinic acidHCID 1784255374-amino-N-hydroxy-6-(methyl-3-methylphenyl-amino)-[1,3,5]triazine-2-carboxamidineHCID 1784821214-Amino-N-hydroxy-6-[methyl(phenyl)amino]-1,3,5-triazine-2-carboximidamide

Product 1

HCID 867105136-[5-(6-chloropyridin-3-yl)-1,2,4-oxadiazol-3-yl]-2-N-methyl-2-N-phenyl-1,3,5-triazine-2,4-diamine

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

6-Chloropyridine-3-carboxylic acid (Ig, 6.35 mmol) and thionyl chloride (10 mL, 138 mmol) were heated to reflux for 2 hours. The mixture was concentrated under vacuum and the residue was azeotroped with diethyl ether and evaporated. A portion of this acid chloride (0.75 g, 4.26 mmol) was then added to a solution of 4-amino-N-hydroxy-6-[methyl(phenyl)amino]-1,3,5-triazine-2-carboximidamide (prepared in an analogous manner to Intermediate 1, 0.920 g, 3.55 mmol) in pyridine (12 mL) and the mixture was stirred at room temperature overnight before being heated to 70 C for 3 h. The mixture was cooled to room temperature and concentrated under vacuum. Water was added and the mixture was stirred for 30 min. The solids were filtered and washed with further water. The solid was then azeotroped with toluene and dried under vacuum to afford the title compound, which was used without purification in the next step. Method B HPLC-MS: MH+ requires m/z=381 Found: m/z=381, Rt=1.99 min (35%).

Workup

  1. temperatureto reflux for 2 hours
  2. concentrationThe mixture was concentrated under vacuum
  3. customthe residue was azeotroped with diethyl ether
  4. customevaporated
  5. temperaturebefore being heated to 70 C for 3 h
  6. temperatureThe mixture was cooled to room temperature
  7. concentrationconcentrated under vacuum
  8. additionWater was added
  9. stirringthe mixture was stirred for 30 min
  10. filtrationThe solids were filtered
  11. washwashed with further water
  12. customThe solid was then azeotroped with toluene
  13. customdried under vacuum

Sources & evidence

ORD record
ord-bb7c1d8743a248be844d7633e9856b94
Source dataset
uspto-grants-2014_11
Patent number
US08895733B2

Reaction notes

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