Potassium Phosphate, Tribasic → 3-(3-(tert-butyldimethylsilyloxy)propyl)-6-(4-chlorophenyl)-5-((4-chlorophenyl)(hydroxy)methyl)-1-methylpyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione

HRID 60155Notes

Reaction equation

HRID 60155 reaction equation
[Si:1]([O:8][CH2:9][CH2:10][CH2:11][N:12]1[C:17](=[O:18])[C:16]2[C:19]([CH:24]([C:26]3[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][CH:27]=3)[OH:25])=[C:20](Cl)[N:21]=[CH:22][C:15]=2[N:14]([CH3:33])[C:13]1=[O:34])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[Cl:35][C:36]1[CH:41]=[CH:40][C:39](B(O)O)=[CH:38][CH:37]=1.C([O-])(O)=O.[Na+].[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Si:1]([O:8][CH2:9][CH2:10][CH2:11][N:12]1[C:17](=[O:18])[C:16]2[C:19]([CH:24]([C:26]3[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][CH:27]=3)[OH:25])=[C:20]([C:39]3[CH:40]=[CH:41][C:36]([Cl:35])=[CH:37][CH:38]=3)[N:21]=[CH:22][C:15]=2[N:14]([CH3:33])[C:13]1=[O:34])([C:4]([CH3:6])([CH3:5])[CH3:7])([CH3:2])[CH3:3]

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 742994-Chlorophenylboronic acidHCID 516892Sodium BicarbonateHCID 1317370763-(3-(tert-butyldimethylsilyloxy)propyl)-6-chloro-5-((4-chlorophenyl) (hydroxy)methyl)-1-methylpyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione2×

Product 1

HCID 1317370753-(3-(tert-butyldimethylsilyloxy)propyl)-6-(4-chlorophenyl)-5-((4-chlorophenyl)(hydroxy)methyl)-1-methylpyrido[3,4-d]pyrimidine-2,4(1H,3H)-dioneYield 20.1%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 3-(3-(tert-butyldimethylsilyloxy)propyl)-6-chloro-5-((4-chlorophenyl) (hydroxy)methyl)-1-methylpyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione (See Compound 49, step 4, 130 mg, 0.248 mmol), 4-chlorophenylboronic acid (77.37 mg, 0.496 mmol), NaHCO3 (62.5 mg, 0.744 mmol) and aq. 2M K3PO4 (0.62 ml, 1.24 mmol) in dioxane (1 mL) and water (0.2 mL) was added Pd(dppf)Cl2 (7 mg, 0.0096 mmol). The reaction was degassed with nitrogen (3×) and heated at 120° C. (MW) for 1.5 h, cooled to RT then diluted with EA (10 mL) and water (2 mL). The reaction was filtered and the filtrate was concentrated to a residue which was purified by Prep TLC eluted with PE/EA (2:1) to give 3-(3-(tert-butyldimethylsilyloxy)propyl)-6-(4-chlorophenyl)-5-((4-chlorophenyl)(hydroxy)methyl)-1-methylpyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione (30 mg, 20% yield) as colorless oil, LCMS: MH+ 600 and TR=2.924 min.

Workup

  1. customThe reaction was degassed with nitrogen (3×)
  2. temperatureheated at 120° C. (MW) for 1.5 h
  3. additionthen diluted with EA (10 mL) and water (2 mL)
  4. filtrationThe reaction was filtered
  5. concentrationthe filtrate was concentrated to a residue which
  6. customwas purified by Prep TLC
  7. washeluted with PE/EA (2:1)

Sources & evidence

ORD record
ord-47078eb14f404ebeb986ee39a0705651
Source dataset
uspto-grants-2016_09
Patent number
US09440973B2

Reaction notes

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