Triethylamine → 8-((4-(4-chloro-3-(trifluoromethyl)phenoxy)phenyl)ethynyl)-1-methyl-3,4-dihydro-1H-pyrimido[1,6-a]pyrimidin-6(2H)-one

HRID 920324

Reaction equation

HRID 920324 reaction equation
C(N(CC)CC)C.[Cl:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][C:16]2[CH:21]=[CH:20][C:19]([C:22]#[CH:23])=[CH:18][CH:17]=2)=[CH:11][C:10]=1[C:24]([F:27])([F:26])[F:25].Cl[C:29]1[CH:39]=[C:33]2[N:34]([CH3:38])[CH2:35][CH2:36][CH2:37][N:32]2[C:31](=[O:40])[N:30]=1>C1COCC1.CCOC(C)=O.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.[Cu]I>[Cl:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][C:16]2[CH:17]=[CH:18][C:19]([C:22]#[C:23][C:29]3[CH:39]=[C:33]4[N:34]([CH3:38])[CH2:35][CH2:36][CH2:37][N:32]4[C:31](=[O:40])[N:30]=3)=[CH:20][CH:21]=2)=[CH:11][C:10]=1[C:24]([F:25])([F:26])[F:27]

Participants

8

Reactant 3

HCID 8471TriethylamineHCID 717434718-Chloro-1-methyl-3,4-dihydro-1H-pyrimido[1,6-A]pyrimidin-6(2H)-oneHCID 866763761-Chloro-4-(4-ethynylphenoxy)-2-(trifluoromethyl)benzene

Product 1

HCID 712365888-((4-(4-chloro-3-(trifluoromethyl)phenoxy)phenyl)ethynyl)-1-methyl-3,4-dihydro-1H-pyrimido[1,6-a]pyrimidin-6(2H)-oneYield 13%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

A suspension of bis(triphenylphosphine)palladium(II) chloride (70.3 mg, 0.1 mmol) and copper(I) iodide (19.1 mg, 0.1 mmol) in anhydrous THF (12 mL), was purged with Ar for 10 mins at rt. The suspension was treated with triethylamine (0.42 mL, 3.0 mmol), and 1-chloro-4-(4-ethynylphenoxy)-2-(trifluoromethyl)benzene (446 mg, 1.5 mmol) was added under an Ar atmosphere, which produced a dark amber color. After 5 mins, 8-chloro-1-methyl-3,4-dihydro-1H-pyrimido[1,6-a]pyrimidin-6(2H)-one (100 mg, 0.5 mmol) was added, and stirred for 2 h at 50° C. The reaction mixture was diluted with EtOAc, washed with water, and then concentrated. The residue was purified by MDAP to afford the title compound (30 mg) as a pale yellow solid.

Workup

  1. customwas purged with Ar for 10 mins at rt
  2. additionwas added under an Ar atmosphere, which
  3. customproduced a dark amber color
  4. washwashed with water
  5. concentrationconcentrated
  6. customThe residue was purified by MDAP

Sources & evidence

ORD record
ord-a660d1c907364c4685d67b3c06e8e494
Source dataset
uspto-grants-2016_03
Patent number
US09273054B2

Linked notes

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