1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → 6-[5-(3-Fluoropyridin-2-yl)-[1,2,4]oxadiazol-3-yl]-N-methyl-N-phenyl-[1,3,5]triazine-2,4-diamine

HRID 341460Notes

Reaction equation

HRID 341460 reaction equation
Cl.CN(C)CCCN=C=NCC.[F:13][C:14]1[C:15]([C:20]([OH:22])=O)=[N:16][CH:17]=[CH:18][CH:19]=1.[NH2:23][C:24]1[N:29]=[C:28]([N:30]([CH3:38])[C:31]2[CH:36]=[CH:35][CH:34]=[C:33](C)[CH:32]=2)[N:27]=[C:26]([C:39]([NH:41]O)=[NH:40])[N:25]=1>N1C=CC=CC=1.CCOC(C)=O>[F:13][C:14]1[C:15]([C:20]2[O:22][N:41]=[C:39]([C:26]3[N:27]=[C:28]([N:30]([CH3:38])[C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)[N:29]=[C:24]([NH2:23])[N:25]=3)[N:40]=2)=[N:16][CH:17]=[CH:18][CH:19]=1

Participants

6

Reactant 3

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride3×HCID 27627863-Fluoropyridine-2-carboxylic acid2×HCID 1784255374-amino-N-hydroxy-6-(methyl-3-methylphenyl-amino)-[1,3,5]triazine-2-carboxamidine2×

Product 1

HCID 569425726-[5-(3-Fluoropyridin-2-yl)-[1,2,4]oxadiazol-3-yl]-N-methyl-N-phenyl-[1,3,5]triazine-2,4-diamine

Reagents, catalysts & solvents 2

HCID 1049PyridineSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

N-[3-(Dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride (633 mg, 3.3 mmol) was added to a solution of 3-fluoropyridine-2-carboxylic acid (400 mg, 2.83 mmol) in anhydrous pyridine (6 mL) in a sealed tube at room temperature under nitrogen. The reaction mixture was stirred at room temperature for 1 h. 4-Amino-N-hydroxy-6-(methyl-3-methylphenyl-amino)-[1,3,5]triazine-2-carboxamidine (prepared in an analogous manner to Intermediate 1, 611 mg, 2.36 mmol) was added and the mixture was stirred at room temperature for approximately 18 h. A solution of N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride (315 mg, 1.15 mmol) in anhydrous pyridine (1 mL) was added and the mixture was stirred for 2 h. Further N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride (100 mg, 0.52 mmol) and 3-fluoropyridine-2-carboxylic acid (70 mg, 0.5 mmol) were then added and the mixture was stirred at room temperature for 1 h and then at 60 C for approximately 18 h. The mixture was then diluted with EtOAc (75 mL) and washed with saturated aq. ammonium chloride (4×15 mL), then saturated aq. sodium bicarbonate (3×15 mL) and brine (15 mL). The organic layer was dried over sodium sulfate and evaporated under vacuum. The crude residue was purified by flash chromatography (0-2% MeOH in DCM) to afford the title compound (220 mg). 20 mg of this material was dissolved in hot DMSO (0.3 mL) and MeOH (0.5 mL) and then 1:1 MeCN:water (1 mL) was added. The resultant precipitate was filtered, the solids were washed with water (2×1 mL) and then dried under vacuum to afford the title compound as a white solid (14 mg, 2%).

Workup

  1. additionwas added
  2. stirringthe mixture was stirred at room temperature for approximately 18 h
  3. stirringthe mixture was stirred for 2 h
  4. stirringthe mixture was stirred at room temperature for 1 h
  5. waitat 60 C for approximately 18 h
  6. washwashed with saturated aq. ammonium chloride (4×15 mL)
  7. dry with materialThe organic layer was dried over sodium sulfate
  8. customevaporated under vacuum
  9. customThe crude residue was purified by flash chromatography (0-2% MeOH in DCM)

Sources & evidence

ORD record
ord-082dff1468cc4009a1ccb7a9712f1bd9
Source dataset
uspto-grants-2014_11
Patent number
US08895733B2

Reaction notes

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