Triethylamine → (E)-4-(2-(1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-yl)vinyl)-N-(4-(trifluoromethyl)phenyl)-1,3,5-triazin-2-amine

HRID 77477Notes

Reaction equation

HRID 77477 reaction equation
I[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][O:12]1)[N:6]=[CH:5]2.[F:17][C:18]([F:35])([F:34])[C:19]1[CH:24]=[CH:23][C:22]([NH:25][C:26]2[N:31]=[C:30]([CH:32]=[CH2:33])[N:29]=[CH:28][N:27]=2)=[CH:21][CH:20]=1.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(N(CC)CC)C>C(#N)C.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]>[O:12]1[CH2:13][CH2:14][CH2:15][CH2:16][CH:11]1[N:7]1[C:8]2[C:4](=[CH:3][C:2](/[CH:33]=[CH:32]/[C:30]3[N:29]=[CH:28][N:27]=[C:26]([NH:25][C:22]4[CH:21]=[CH:20][C:19]([C:18]([F:34])([F:17])[F:35])=[CH:24][CH:23]=4)[N:31]=3)=[CH:10][CH:9]=2)[CH:5]=[N:6]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 80271Tri-o-tolylphosphineHCID 667934695-Iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazoleHCID 86679766N-(4-(trifluoromethyl)phenyl)-4-vinyl-1,3,5-triazin-2-amine

Product 1

HCID 86679767(E)-4-(2-(1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-yl)vinyl)-N-(4-(trifluoromethyl)phenyl)-1,3,5-triazin-2-amineYield 56.4%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
90 °C

Procedure

To a stirred solution of 5-iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (0.05 g, 0.152 mmol) in ACN (5 mL) were added N-(4-(trifluoromethyl)phenyl)-4-vinyl-1,3,5-triazin-2-amine (0.041 g, 0.152 mmol), tri-o-tolylphosphine (0.019 g, 0.061 mmol) and triethylamine (0.064 mL, 0.457 mmol). Nitrogen was purged for 5 minutes. Tris(dibenzylideneacetone)dipalladium(0) (0.014 g, 0.015 mmol) was added and the reaction mixture was heated at 90° C. overnight. The reaction mixture was filtered through a pad of celite, washed with ethyl acetate, and the organic layer was concentrated. The crude product was purified by flash chromatography on silica gel using 25% ethyl acetate in hexane to give (E)-4-(2-(1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-yl)vinyl)-N-(4-(trifluoromethyl)phenyl)-1,3,5-triazin-2-amine as a pale yellow solid (0.04 g, 42% yield). LCMS: R.T.=1.21 min; [M+H]+=467.33.

Workup

  1. customNitrogen was purged for 5 minutes
  2. filtrationThe reaction mixture was filtered through a pad of celite
  3. washwashed with ethyl acetate
  4. concentrationthe organic layer was concentrated
  5. customThe crude product was purified by flash chromatography on silica gel using 25% ethyl acetate in hexane

Sources & evidence

ORD record
ord-547cb35abe2a4d62b3ab7f5657fc4139
Source dataset
uspto-grants-2014_09
Patent number
US08841301B2

Reaction notes

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