Potassium Phosphate, Tribasic → HCID 118863133, compound

HRID 63893Notes

Reaction equation

HRID 63893 reaction equation
Br[C:2]1[S:23][C:5]2[N:6]([CH3:22])[C:7](=[O:21])[N:8]([CH2:11][CH2:12][CH2:13][O:14][CH:15]3[CH2:20][CH2:19][CH2:18][CH2:17][O:16]3)[C:9](=[O:10])[C:4]=2[C:3]=1[CH:24]([C:26]1[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][CH:27]=1)[OH:25].[Cl:33][C:34]1[CH:35]=[C:36](B(O)O)[CH:37]=[CH:38][CH:39]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.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:33][C:34]1[CH:39]=[C:38]([C:2]2[S:23][C:5]3[N:6]([CH3:22])[C:7](=[O:21])[N:8]([CH2:11][CH2:12][CH2:13][O:14][CH:15]4[CH2:20][CH2:19][CH2:18][CH2:17][O:16]4)[C:9](=[O:10])[C:4]=3[C:3]=2[CH:24]([C:26]2[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][CH:27]=2)[OH:25])[CH:37]=[CH:36][CH:35]=1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 2734323(3-Chlorophenyl)boronic acidHCID 1188631046-bromo-5-((4-chlorophenyl) (hydroxy)methyl)-1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione

Product 1

HCID 118863133HCID 118863133, compoundYield 76.4%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
85 °C

Procedure

To a solution of 6-bromo-5-((4-chlorophenyl)(hydroxy)methyl)-1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione (50 mg, 0.091 mmol), (3-chlorophenyl)boronic acid (28.7 mg, 0.183 mmol) and aq. 2 M K3PO4 (0.4 mL) in dioxane (2 mL) was added Pd(PPh3)4 (10 mg). The reaction was heated at 85° C. for 2 h, cooled to RT, filtered and the filtrate was diluted DCM (10 mL) and water (10 mL). The organic layer was dried over Na2SO4 and concentrated to a residue which was purified by chromatography eluted with PE/EA (10:1 to 3:1) to give 6-(3-chlorophenyl)-5-((4-chlorophenyl)(hydroxy)methyl)-1-methyl-3-(3-((tetra hydro-2H-pyran-2-yl)oxy)propyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione (40 mg, 75.6% yield) as a solid. LCMS: [M+-THP-OH] 473 and TR=2.215 min.

Workup

  1. temperaturecooled to RT
  2. filtrationfiltered
  3. dry with materialThe organic layer was dried over Na2SO4
  4. concentrationconcentrated to a residue which
  5. customwas purified by chromatography
  6. washeluted with PE/EA (10:1 to 3:1)

Sources & evidence

ORD record
ord-540f3177e2fd42899dd0f28b04f35f09
Source dataset
uspto-grants-2016_09
Patent number
US09447114B2

Reaction notes

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