N,N,N',N'-Tetramethylethylenediamine → 1-(4-(2-Hydroxy-2-methylpropoxy)-3-methoxyphenyl)-4-(phenylethynyl)pyrimidin-2(1H)-one

HRID 2059849Notes

Reaction equation

HRID 2059849 reaction equation
[C:1]1([C:7]#[C:8][C:9]2[CH:14]=[CH:13][NH:12][C:11](=[O:15])[N:10]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH:16][C:17]([CH3:32])([CH3:31])[CH2:18][O:19][C:20]1[CH:25]=[CH:24][C:23](B(O)O)=[CH:22][C:21]=1[O:29][CH3:30].CN(C)CCN(C)C.C(OC)(C)(C)C>CO.O.C(Cl)Cl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[OH:16][C:17]([CH3:32])([CH3:31])[CH2:18][O:19][C:20]1[CH:25]=[CH:24][C:23]([N:12]2[CH:13]=[CH:14][C:9]([C:8]#[C:7][C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)=[N:10][C:11]2=[O:15])=[CH:22][C:21]=1[O:29][CH3:30]

Participants

9

Reactant 4

HCID 8037N,N,N',N'-TetramethylethylenediamineHCID 15413tert-Butyl methyl etherHCID 585798634-(2-Hydroxy-2-methylpropoxy)-3-methoxyphenylboronic acidHCID 178517722HCID 178517722, compound

Product 1

HCID 469270441-(4-(2-Hydroxy-2-methylpropoxy)-3-methoxyphenyl)-4-(phenylethynyl)pyrimidin-2(1H)-oneYield 37%

Reagents, catalysts & solvents 4

HCID 8895Cupric acetateCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred mixture of 4-(phenylethynyl)pyrimidin-2(1H)-one Part B (20 mg, 0.1 mmol), 4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenylboronic acid Part D (48.9 mg, 0.2 mmol), and copper (II) acetate (18.5 mg, 0.1 mmol) in MeOH (2 mL) and H2O (0.5 mL) was added N1,N1,N2,N2-tetramethylethane-1,2-diamine (24 mg, 0.2 mmol) at RT. The reaction mixture was stirred at RT for 45 min under oxygen, diluted with CH2Cl2, washed sequentially with 5% aq. H2SO4 and sat. NaHCO3. The organic phase was dried (MgSO4), concentrated, and the residue was subjected to flash chromatography (silica gel/hexane-EtOAc 100:0 to 0:100 gradient) to afford impure product. Trituration with methyl t-butyl ether yielded the title compound B-1 (15 mg, 0.038 mmol, 37% yield) as a pure solid. LC/MS 391 (M+H)+, tR 0.82 min (method 5); 1H NMR (400 MHz, chloroform-D) δ 7.70 (1H, d, J=6.78 Hz), 7.51-7.66 (2H, m), 7.37-7.47 (3H, m), 6.95-7.12 (2H, m), 6.90 (1H, dd, J=8.53, 2.51 Hz), 6.54 (1H, d, J=6.78 Hz), 3.88 (3H, s), 3.85 (2H, s), 1.36 (6H, s).

Workup

  1. washwashed sequentially with 5% aq. H2SO4 and sat. NaHCO3
  2. dry with materialThe organic phase was dried (MgSO4)
  3. concentrationconcentrated
  4. customto afford impure product

Sources & evidence

ORD record
ord-493733559b1f4f92a1b2af2641976923
Source dataset
uspto-grants-2012_10
Patent number
US08278316B2

Reaction notes

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