Diisopropylethylamine → 2-N-Phenyl-6-(5-{4-[(2,2,2-trifluoroethoxy)methyl]piperidin-1-yl}-1,2,4-oxadiazol-3-yl)-1,3,5-triazine-2,4-diamine

HRID 341424Notes

Reaction equation

HRID 341424 reaction equation
[C:1]1([NH:7][C:8]2[N:13]=[C:12]([NH2:14])[N:11]=[C:10]([C:15]3[N:19]=[C:18](C(Cl)(Cl)Cl)[O:17][N:16]=3)[N:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CCN(C(C)C)C(C)C.Cl.[F:34][C:35]([F:46])([F:45])[CH2:36][O:37][CH2:38][CH:39]1[CH2:44][CH2:43][NH:42][CH2:41][CH2:40]1>CN(C=O)C>[C:1]1([NH:7][C:8]2[N:13]=[C:12]([NH2:14])[N:11]=[C:10]([C:15]3[N:19]=[C:18]([N:42]4[CH2:41][CH2:40][CH:39]([CH2:38][O:37][CH2:36][C:35]([F:34])([F:45])[F:46])[CH2:44][CH2:43]4)[O:17][N:16]=3)[N:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 457917814-((2,2,2-Trifluoroethoxy)methyl)piperidine hydrochloride2×HCID 668025602-N-phenyl-6-[5-(trichloromethyl)-1,2,4-oxadiazol-3-yl]-1,3,5-triazine-2,4-diamine2×

Product 1

HCID 668022332-N-Phenyl-6-(5-{4-[(2,2,2-trifluoroethoxy)methyl]piperidin-1-yl}-1,2,4-oxadiazol-3-yl)-1,3,5-triazine-2,4-diamineYield 8.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To 2-N-phenyl-6-[5-(trichloromethyl)-1,2,4-oxadiazol-3-yl]-1,3,5-triazine-2,4-diamine (Intermediate 134, 0.100 g, 0.268 mmol) in DMF (2 mL) was added DIPEA (93.6 μL, 0.537 mmol) at the mixture was stirred at room temperature for 5 min. 4-[(2,2,2-trifluoroethoxy)methyl]piperidine hydrochloride (Intermediate 179, 0.063 g, 0.268 mmol) was added and the mixture was stirred at room temperature for 18 h. The reaction mixture was then heated to 50 C for 18 h and to 70 C for 36 h. The reaction mixture was concentrated under reduced pressure, dissolved in EtOAc and washed with water. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The crude compound was purified by preparative HPLC, Method C, to afford the title compound (10.8 mg, 8.9%).

Workup

  1. stirringthe mixture was stirred at room temperature for 18 h
  2. temperatureThe reaction mixture was then heated to 50 C for 18 h and to 70 C for 36 h
  3. concentrationThe reaction mixture was concentrated under reduced pressure
  4. dissolutiondissolved in EtOAc
  5. washwashed with water
  6. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe crude compound was purified by preparative HPLC, Method C

Sources & evidence

ORD record
ord-40c684f7ff0a4564a4761e0c7bcf67c5
Source dataset
uspto-grants-2014_11
Patent number
US08895733B2

Reaction notes

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