4-Bromotoluene → 7-(p-Tolyl)-N-(4-(trifluoromethyl)phenyl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-amine

HRID 971245Notes

Reaction equation

C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.Br[C:48]1[CH:53]=[CH:52][C:51]([CH3:54])=[CH:50][CH:49]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[F:61][C:62]([F:81])([F:80])[C:63]1[CH:68]=[CH:67][C:66]([NH:69][C:70]2[C:71]3[CH2:79][CH2:78][NH:77][CH2:76][C:72]=3[N:73]=[CH:74][N:75]=2)=[CH:65][CH:64]=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCOCC1>[C:51]1([CH3:54])[CH:52]=[CH:53][C:48]([N:77]2[CH2:78][CH2:79][C:71]3[C:70]([NH:69][C:66]4[CH:65]=[CH:64][C:63]([C:62]([F:81])([F:61])[F:80])=[CH:68][CH:67]=4)=[N:75][CH:74]=[N:73][C:72]=3[CH2:76]2)=[CH:49][CH:50]=1

Participants

Conditions

Temperature: 160 °C

Procedure

To 2 mL of dioxane was added 10 mol % of palladium(II)acetate (12 mg) and 20 mol % rac-BINAP (58 mg). After stirring for 3 hours, 4-bromotoluene (90 mg, 0.53 mmol), cesium carbonate (682 mg, 2.12 mmol), N-(4-(Trifluoromethyl)phenyl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-amine (150 mg, 0.51 mmol) and activated molecular sieves (340 mg) were added. The mixture was sonicated for 10 minutes and heated in a sealed tube via microwave at 160° C. for 3 hours in a Personal Chemistry Microwave (Smith Creator). After completion, the mixture was filtered through celite, evaporated and purified by flash chromatography over silica gel using a 0-100% gradient of ethyl acetate/hexanes to give the desired product as a white solid (34 mg).

Workup

customThe mixture was sonicated for 10 minutes
filtrationAfter completion, the mixture was filtered through celite
customevaporated
custompurified by flash chromatography over silica gel using a 0-100% gradient of ethyl acetate/hexanes

Sources & evidence

ORD record: ord-b7b10d5f8c8c436a885c4d1b097181fe
Source dataset: uspto-grants-2007_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07312330B2

Reaction notes

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