Potassium Carbonate → (1S)-N-{[2-(2,6-diethylphenyl)-4-methoxy-6-methylpyrimidin-5-yl]methyl}-N-methyl-1,2,3,4-tetrahydronaphthalen-1-amine

HRID 1091928Notes

Reaction equation

HRID 1091928 reaction equation
Cl[C:2]1[N:7]=[C:6](Cl)[C:5]([CH2:9][N:10]([CH3:21])[C@@H:11]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[CH2:14][CH2:13][CH2:12]2)=[C:4]([CH3:22])[N:3]=1.[O:23]1[CH2:28]COCC1.[CH2:29]([C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([CH2:37][CH3:38])[C:32]=1B(O)O)[CH3:30].C([O-])([O-])=O.[K+].[K+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O.CCOC(C)=O>[CH2:29]([C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([CH2:37][CH3:38])[C:32]=1[C:2]1[N:7]=[C:6]([O:23][CH3:28])[C:5]([CH2:9][N:10]([CH3:21])[C@@H:11]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[CH2:14][CH2:13][CH2:12]2)=[C:4]([CH3:22])[N:3]=1)[CH3:30]

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 18437832(2,6-Diethylphenyl)boronic acidHCID 57531525(1S)-(2,4-Dichloro-6-methyl-pyrimidin-5-ylmethyl)methyl-(1,2,3,4-tetrahydro-naphthalen-1-yl)-amine

Product 1

HCID 57531359(1S)-N-{[2-(2,6-diethylphenyl)-4-methoxy-6-methylpyrimidin-5-yl]methyl}-N-methyl-1,2,3,4-tetrahydronaphthalen-1-amine

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a sealed tube containing (1S)-(2,4-dichloro-6-methyl-pyrimidin-5-ylmethyl)-methyl-(1,2,3,4-tetrahydro-naphthalen-1-yl)-amine (3.4 g, 10.25 mmol) is added dioxane (40 mL), 2,6-diethylphenylboronic acid (3.65 g, 2.0 eq., 20.5 mmol) and K2CO3 (5.7 g, 4.0 eq., 41 mmol dissolved in 10 mL water) under a nitrogen atmosphere. Pd(PPh3)4 (5 mol %, 590 mg) is added and after sealing is allowed to react at 95° C. for 16 h. After cooling to room temperature, EtOAc (100 mL) and water (100 mL) is added and the organic layer is washed with sat. NaHCO3 (100 mL), brine (100 mL) and dried over Na2SO4. The crude sample is purified by SiO2 flash chromatography using hexanes:Et2O 5:1 with 1.0% triethylamine to recover the title compound as a colorless oil. [mass expected (429.60); mass found (429.33)]

Workup

  1. customto react at 95° C. for 16 h
  2. washthe organic layer is washed with sat. NaHCO3 (100 mL), brine (100 mL)
  3. dry with materialdried over Na2SO4
  4. customThe crude sample is purified by SiO2 flash chromatography
  5. customto recover the title compound as a colorless oil

Sources & evidence

ORD record
ord-493c7bc89cb44fecae718a2c017789b0
Source dataset
uspto-grants-2012_03
Patent number
US08129395B2

Reaction notes

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