Potassium Phosphate, Tribasic → HCID 46927505, compound

HRID 2059867Notes

Reaction equation

HRID 2059867 reaction equation
Cl[C:2]1[N:7]=[CH:6][N:5]([C:8]2[CH:13]=[CH:12][C:11]([O:14][CH2:15][C:16]([OH:19])([CH3:18])[CH3:17])=[C:10]([O:20][CH3:21])[CH:9]=2)[C:4](=[O:22])[CH:3]=1.[Cl:23][C:24]1[CH:34]=[CH:33][C:27](/[CH:28]=[CH:29]/B(O)O)=[CH:26][CH:25]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C.C(Cl)Cl.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>[Cl:23][C:24]1[CH:34]=[CH:33][C:27](/[CH:28]=[CH:29]/[C:2]2[N:7]=[CH:6][N:5]([C:8]3[CH:13]=[CH:12][C:11]([O:14][CH2:15][C:16]([OH:19])([CH3:18])[CH3:17])=[C:10]([O:20][CH3:21])[CH:9]=3)[C:4](=[O:22])[CH:3]=2)=[CH:26][CH:25]=1

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 642694trans-2-(4-Chlorophenyl)vinylboronic acidHCID 585799166-chloro-3-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)-pyrimidin-4(3H)-one

Product 1

HCID 46927505HCID 46927505, compoundYield 31%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
55 °C

Procedure

A mixture of 6-chloro-3-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)pyrimidin-4(3H)-one Part A of Procedure 11 (40 mg, 0.12 mmol), (E)-4-chlorostyrylboronic acid (56 mg, 0.30 mmol), potassium phosphate, tribasic (78 mg, 0.37 mmol), and palladiumtetrakis (7 mg, 6.16 μmol) in DMF (1 mL) was stirred under nitrogen at 55° C. for 1 hour. The mixture was diluted with DCM, washed with water, sat. NaHCO3 and brine, then dried (Na2SO4) and concentrated to afford the crude product. The crude product was purified using ISCO flash chromatography (silica gel/hexanes-ethyl acetate 100:0 to 0:100 gradient). The product was re-purified using HPLC (C18 column/10:90 to 90:10 MeOH—H2O) to afford the desired product (E)-6-(4-chlorostyryl)-3-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)pyrimidin-4(3H)-one J-1 (16.8 mg, 0.039 mmol, 31% yield) as a light yellow solid. LC/MS 427 (M+H)+, tR 0.97 min (method 5); 1H NMR (400 MHz, CHLOROFORM-d) δ 8.15 (1H, s), 7.76 (1H, d, J=15.56 Hz), 7.53 (2H, d, J=8.28 Hz), 7.38 (2H, d, J=8.28 Hz), 7.01 (1H, d, J=8.03 Hz), 6.82-6.98 (3H, m), 6.46 (1H, s), 3.89 (5H, br. s.), 1.37 (6H, s).

Workup

  1. washwashed with water, sat. NaHCO3 and brine
  2. dry with materialdried (Na2SO4)
  3. concentrationconcentrated
  4. customto afford the crude product
  5. customThe crude product was purified
  6. customThe product was re-purified

Sources & evidence

ORD record
ord-2017c4986555429a9f396e2422ec9401
Source dataset
uspto-grants-2012_10
Patent number
US08278316B2

Reaction notes

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