Ethanamine, 2,2,2-trifluoro- → 2-N-Methyl-2-N-phenyl-6-(5-{6-[(2,2,2-trifluoroethyl)amino]pyridin-3-yl}-1,2,4-oxadiazol-3-yl)-1,3,5-triazine-2,4-diamine

HRID 341442Notes

Reaction equation

HRID 341442 reaction equation
CN(C1C(C2C(P(C3CCCCC3)C3CCCCC3)=CC=CC=2)=CC=CC=1)C.Cl[C:30]1[N:35]=[CH:34][C:33]([C:36]2[O:40][N:39]=[C:38]([C:41]3[N:46]=[C:45]([N:47]([CH3:54])[C:48]4[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=4)[N:44]=[C:43]([NH2:55])[N:42]=3)[N:37]=2)=[CH:32][CH:31]=1.[F:56][C:57]([F:61])([F:60])[CH2:58][NH2:59].[Li+].C[Si]([N-][Si](C)(C)C)(C)C>C1COCC1.CCOC(C)=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:54][N:47]([C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1)[C:45]1[N:44]=[C:43]([NH2:55])[N:42]=[C:41]([C:38]2[N:37]=[C:36]([C:33]3[CH:34]=[N:35][C:30]([NH:59][CH2:58][C:57]([F:61])([F:60])[F:56])=[CH:31][CH:32]=3)[O:40][N:39]=2)[N:46]=1

Participants

8

Reactant 4

HCID 9773Ethanamine, 2,2,2-trifluoro-HCID 2733832Lithium HexamethyldisilazideHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 867105136-[5-(6-chloropyridin-3-yl)-1,2,4-oxadiazol-3-yl]-2-N-methyl-2-N-phenyl-1,3,5-triazine-2,4-diamine2×

Product 1

HCID 668024012-N-Methyl-2-N-phenyl-6-(5-{6-[(2,2,2-trifluoroethyl)amino]pyridin-3-yl}-1,2,4-oxadiazol-3-yl)-1,3,5-triazine-2,4-diamineYield 6%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

DavePhos (2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl, 0.023 g, 0.058 mmol) and tris(dibenzylideneacetone)dipalladium(0) (0.024 g, 0.026 mmol) were added to a mixture of 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 (Intermediate 135, 0.100 g, 0.263 mmol) and 2,2,2-trifluoroethan-1-amine (0.084 mL, 1.050 mmol) in THF (1 mL) under nitrogen at room temperature. The reaction mixture was degassed by nitrogen bubbling and a 1M solution of LiHMDS in THF (2.10 mL, 2.10 mmol) was added drop wise at room temperature. The reaction mixture was heated under microwave conditions (200 W, T=120 C) for 40 min (20 min ramp, 20 min at 120 C) while being stirred. At room temperature the reaction mixture was diluted with EtOAc and filtered. The collected solid was taken in MeOH, filtered and wash with a large amount of MeOH and further purified by preparative HPLC, to afford the title compound (7 mg, 6%).

Workup

  1. customThe reaction mixture was degassed by nitrogen bubbling
  2. temperatureThe reaction mixture was heated under microwave conditions (200 W, T=120 C) for 40 min (20 min ramp, 20 min at 120 C)
  3. filtrationfiltered
  4. filtrationfiltered
  5. washwash with a large amount of MeOH
  6. customfurther purified by preparative HPLC

Sources & evidence

ORD record
ord-f2738aa5832a4f299209c9f748440930
Source dataset
uspto-grants-2014_11
Patent number
US08895733B2

Reaction notes

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