Potassium Phosphate, Tribasic → 6-(3,4-dichlorophenyl)-3-(3-hydroxypropyl)-1,5-dimethylthieno[2,3-d]pyrimidine-2,4(1H,3H)-dione

HRID 63897Notes

Reaction equation

HRID 63897 reaction equation
Br[C:2]1[S:17][C:5]2[N:6]([CH3:16])[C:7](=[O:15])[N:8]([CH2:11][CH2:12][CH2:13][OH:14])[C:9](=[O:10])[C:4]=2[C:3]=1[CH3:18].[Cl:19][C:20]1[CH:21]=[C:22](B(O)O)[CH:23]=[CH:24][C:25]=1[Cl:26].[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.CC(=O)OCC.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:19][C:20]1[CH:21]=[C:22]([C:2]2[S:17][C:5]3[N:6]([CH3:16])[C:7](=[O:15])[N:8]([CH2:11][CH2:12][CH2:13][OH:14])[C:9](=[O:10])[C:4]=3[C:3]=2[CH3:18])[CH:23]=[CH:24][C:25]=1[Cl:26]

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 27343303,4-Dichlorobenzeneboronic acidHCID 1188631236-bromo-3-(3-hydroxypropyl)-1,5-dimethylthieno[2,3-d]pyrimidine-2,4(1H,3H)-dione

Product 1

HCID 1188630956-(3,4-dichlorophenyl)-3-(3-hydroxypropyl)-1,5-dimethylthieno[2,3-d]pyrimidine-2,4(1H,3H)-dioneYield 27.4%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
85 °C

Procedure

To a solution of 6-bromo-3-(3-hydroxypropyl)-1,5-dimethylthieno[2,3-d]pyrimidine-2,4(1H,3H)-dione (50 mg, 0.15 mmol) in dioxane (2 mL) was added 3,4-dichlorophenylboronic acid (57.3 mg, 0.3 mmol), Pd(PPh3)4 (17.3 mg, 0.015 mmol) and aq. 2M K3PO4 (0.4 mL). The reaction was heated at 85° C. for 1 h, cooled to RT then diluted with EA (20 mL). The organic layer was washed with brine (20 mL) and aq. NH4Cl (20 mL), dried with Na2SO4 and concentrated to a residue which was purified by Prep HPLC to give 6-(3,4-dichlorophenyl)-3-(3-hydroxypropyl)-1,5-dimethylthieno[2,3-d]pyrimidine-2,4(1H,3H)-dione (15.0 mg, 27.4% yield) as a white solid. 1H NMR (CDCl3) δ: 7.55-7.48 (m, 2H), 7.24 (d, J=2.1 Hz, 1H), 4.27-4.14 (m, 2H), 3.60-3.50 (m, 5H), 3.27 (t, J=6.5 Hz, 1H), 2.54 (s, 3H), 2.00-1.85 (m, 2H). LCMS: MH+ 399 and TR=3.000 min.

Workup

  1. temperaturecooled to RT
  2. washThe organic layer was washed with brine (20 mL) and aq. NH4Cl (20 mL)
  3. dry with materialdried with Na2SO4
  4. concentrationconcentrated to a residue which
  5. customwas purified by Prep HPLC

Sources & evidence

ORD record
ord-7953b887094941508f48dae4311607fe
Source dataset
uspto-grants-2016_09
Patent number
US09447114B2

Reaction notes

Loading…