Tri-o-tolylphosphine → (E)-5-(4-(benzyloxy)styryl)-N-(4-(difluoromethoxy)phenyl)pyrimidin-2-amine

HRID 77489

Reaction equation

HRID 77489 reaction equation
[F:1][CH:2]([F:19])[O:3][C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11]2[N:16]=[CH:15][C:14]([CH:17]=[CH2:18])=[CH:13][N:12]=2)=[CH:6][CH:5]=1.[CH2:20]([O:27][C:28]1[CH:33]=[CH:32][C:31](I)=[CH:30][CH:29]=1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>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.C(Cl)(Cl)Cl.[Pd].[Pd]>[CH2:20]([O:27][C:28]1[CH:33]=[CH:32][C:31](/[CH:18]=[CH:17]/[C:14]2[CH:15]=[N:16][C:11]([NH:10][C:7]3[CH:8]=[CH:9][C:4]([O:3][CH:2]([F:1])[F:19])=[CH:5][CH:6]=3)=[N:12][CH:13]=2)=[CH:30][CH:29]=1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

6

Reactant 3

HCID 80271Tri-o-tolylphosphineHCID 5196711-(Benzyloxy)-4-iodobenzeneHCID 86679783N-(4-(difluoromethoxy)phenyl)-5-vinylpyrimidin-2-amine

Product 1

HCID 86679782(E)-5-(4-(benzyloxy)styryl)-N-(4-(difluoromethoxy)phenyl)pyrimidin-2-amineYield 70%

Reagents, catalysts & solvents 2

HCID 11029508Palladium, tris[mu-[(1,2-eta:4,5-eta)-(1E,4E)-1,5-diphenyl-1,4-pentadien-3-one]]di-, compd. with trichloromethane (1:1)CatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of N-(4-(difluoromethoxy)phenyl)-5-vinylpyrimidin-2-amine (0.102 g, 0.387 mmol) in ACN (3 mL) were added 1-(benzyloxy)-4-iodobenzene (0.1 g, 0.322 mmol), tris(dibenzylideneacetone)dipalladium(0) chloroform adduct (0.033 g, 0.032 mmol), tri-o-tolylphosphine (0.039 g, 0.129 mmol), and TEA (0.135 mL, 0.967 mmol). The reaction mixture was flushed with N2 and heated at 90° C. overnight. Solvent was evaporated, and the residue was dissolved in ethyl acetate, filtered through celite and concentrated. The crude product was purified by flash chromatography on silica gel using 30% ethyl acetate in hexanes to give (E)-5-(4-(benzyloxy)styryl)-N-(4-(difluoromethoxy)phenyl)pyrimidin-2-amine (0.1 g, 70%). 1H NMR (400 MHz, DMSO-d6) δ ppm 5.14 (s, 2H), 6.93-7.30 (m, 7H), 7.34-7.52 (m, 2H), 7.78-7.80 (m, 2H), 8.71 (s, 2H), 9.82 (s, 1H). LCMS: RT 1.18 min, (M+H)+446.6.

Workup

  1. customThe reaction mixture was flushed with N2
  2. customSolvent was evaporated
  3. dissolutionthe residue was dissolved in ethyl acetate
  4. filtrationfiltered through celite
  5. concentrationconcentrated
  6. customThe crude product was purified by flash chromatography on silica gel using 30% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-dce1644f735941578e3238b2fd93288c
Source dataset
uspto-grants-2014_09
Patent number
US08841301B2

Linked notes

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