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

HRID 341454Notes

Reaction equation

HRID 341454 reaction equation
[F:1][C:2]([F:15])([F:14])[CH2:3][O:4][C:5]1[N:10]=[CH:9][C:8]([C:11]([OH:13])=O)=[CH:7][CH:6]=1.Cl.CN(C)CCCN=C=NCC.[NH2:28][C:29]1[N:34]=[C:33]([N:35]([C:37]2[CH:38]=[N:39][C:40]([F:43])=[CH:41][CH:42]=2)[CH3:36])[N:32]=[C:31]([C:44](=[N:46]O)[NH2:45])[N:30]=1>N1C=CC=CC=1.CCOC(C)=O>[F:43][C:40]1[N:39]=[CH:38][C:37]([N:35]([CH3:36])[C:33]2[N:34]=[C:29]([NH2:28])[N:30]=[C:31]([C:44]3[N:45]=[C:11]([C:8]4[CH:9]=[N:10][C:5]([O:4][CH2:3][C:2]([F:1])([F:15])[F:14])=[CH:6][CH:7]=4)[O:13][N:46]=3)[N:32]=2)=[CH:42][CH:41]=1

Participants

6

Reactant 3

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride3×HCID 27810286-(2,2,2-Trifluoroethoxy)pyridine-3-carboxylic acidHCID 1363771384-Amino-6-[(6-fluoropyridin-3-yl)(methyl)amino]-N'-hydroxy-1,3,5-triazine-2-carboximidamide2×

Product 1

HCID 668030012-N-(6-Fluoropyridin-3-yl)-2-N-methyl-6-{5-[6-(2,2,2-trifluoroethoxy)pyridin-3-yl]-1,2,4-oxadiazol-3-yl}-1,3,5-triazine-2,4-diamineYield 3%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8857Ethyl AcetateSolvent

Procedure

6-(2,2,2-Trifluoroethoxy)pyridine-3-carboxylic acid (prepared in an analogous manner to Intermediate 206, 0.216 g, 0.051 mmol) was added to a solution of N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.049 g, 0.252 mmol) in pyridine (1 mL) and the mixture was stirred at room temperature for 16 h. Further N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.0255 g, 0.1 mmol) was added and the mixture was stirred at 50 C for 4 h. 4-Amino-6-[(6-fluoropyridin-3-yl)(methyl)amino]-N′-hydroxy-1,3,5-triazine-2-carboximidamide (Intermediate 156, 0.05 g, 0.18 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.0163 g, 0.09 mmol) were added and the mixture was stirred at 50 C for 16 h and then at 60 C for 5 h. The mixture was dissolved in EtOAc and washed with water, and then saturated aq. ammonium chloride, saturated aq. sodium bicarbonate and then brine. The organic layer was dried over sodium sulfate and concentrated under vacuum. The residue was purified by preparative HPLC, Method B, to afford the title compound (0.002 g, 3%).

Workup

  1. stirringthe mixture was stirred at 50 C for 4 h
  2. stirringthe mixture was stirred at 50 C for 16 h
  3. waitat 60 C for 5 h
  4. washwashed with water
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. concentrationconcentrated under vacuum
  7. customThe residue was purified by preparative HPLC, Method B

Sources & evidence

ORD record
ord-26c073fecba246dd862f16b7f8ee2eca
Source dataset
uspto-grants-2014_11
Patent number
US08895733B2

Reaction notes

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