Triethylamine → 1-(1-Methylpiperidin-4-yl)-7-(pyrimid-5-yl)-naphthalene

HRID 399447Notes

Reaction equation

HRID 399447 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([C:8]2[C:17]3[C:12](=[CH:13][CH:14]=[C:15](OS(C(F)(F)F)(=O)=O)[CH:16]=3)[CH:11]=[CH:10][CH:9]=2)[CH2:4][CH2:3]1.C[Sn](C)(C)[C:28]1[CH:29]=[N:30][CH:31]=[N:32][CH:33]=1.C(N(CC)CC)C.[Cl-].[Li+]>CN(C)C=O.C(OCC)(=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([C:8]2[C:17]3[C:12](=[CH:13][CH:14]=[C:15]([C:28]4[CH:29]=[N:30][CH:31]=[N:32][CH:33]=4)[CH:16]=3)[CH:11]=[CH:10][CH:9]=2)[CH2:4][CH2:3]1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 433294Lithium ChlorideHCID 127998215-Trimethylstannyl-pyrimidineHCID 221156371-(1-Methylpiperidin-4-yl)-7-trifluoromethylsulfonyloxynaphthalene

Product 1

HCID 221157411-(1-Methylpiperidin-4-yl)-7-(pyrimid-5-yl)-naphthalene

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
115 °C

Procedure

A mixture of 1-(1-methylpiperidin-4-yl)-7-trifluoromethanesulfonyloxynaphthalene (0.304 g, 0.819 mmol), 5-trimethylstannylpyrimidine (0.220 g, 0.905 mmol), triethylamine (0.55 mL, 3.95 mmol), lithium chloride (0.107 g, 2.53 mmol), bis(triphenylphosphine)palladium chloride (0.029 g, 0.041 mmol), and butylated hydroxytoluene (BHT, approx. 0.01 g, antioxidant) in dimethylformamide (15 mL) was heated to 115° C. for 1 hour. The reaction was cooled and diluted with ethyl acetate. The mixture was extracted with a mixture of 1N lithium chloride (25 mL) and 1N sodium hydroxide (3 mL), 1N lithium chloride and brine. The organic phase was dried over calcium sulfate and concentrated. The residue was flash chromatographed on silica gel (1×2.5 inches packed with 75% ethyl acetate/hexane). Elution proceeded as follows: 75% ethyl acetate/hexane, 225 mL, nil; ethyl acetate, 200 mL, nil; 1% methanol/ethyl acetate, 200 mL, nil; 5% methanol/ethyl acetate, 300 mL, nil; and 7% methanol/1% triethylamine/ethyl acetate, 250 mL, 0.130 g (52%) of 1-(1-methylpiperidin-4-yl)-7-pyrimid-5-yl-naphthalene as a tan foam. A sample triturated with ether afforded white crystals which had: Mp 121.5°-123° C.; 1H NMR (250 MHz, CDCl3) δ 9.27 (s, 1H), 9.08 (s, 2H), 8.26 (s, 1 H), 8.03 (d, J=8.5 Hz, 1H), 7.78 (dd, J=3, 6.5 Hz, 1H), 7.69 (dd, J=1.5, 8.5 Hz, 1H), 7.57-7.50 (m, 2H), 3.36 (sym m, 1H), 3.09 (br d, J=12 Hz, 2H), 2.40 (s, 3H), 2.28 (sym m, 2H), 2.06-1.90 (m, 4H). Analysis calculated for C20H21N3 : C, 79.17; H, 6.98;N, 13.85. Found: C, 78.46; H, 7.14; N, 13.89. HRMS m/e 303.1731. Observed m/e 303.1700.

Workup

  1. temperatureThe reaction was cooled
  2. extractionThe mixture was extracted with a mixture of 1N lithium chloride (25 mL) and 1N sodium hydroxide (3 mL), 1N lithium chloride and brine
  3. dry with materialThe organic phase was dried over calcium sulfate
  4. concentrationconcentrated
  5. customchromatographed on silica gel (1×2.5 inches packed with 75% ethyl acetate/hexane)
  6. washElution
  7. customA sample triturated with ether afforded white crystals which

Sources & evidence

ORD record
ord-017f6186df31457eabd5f2b2afacab06
Source dataset
uspto-grants-1998_10
Patent number
US05821245

Reaction notes

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