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

HRID 60158Notes

Reaction equation

HRID 60158 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]([OH:29])[CH2:25][CH:26]([CH3:28])[CH3:27])=[C:20](Cl)[N:21]=[CH:22][C:15]=2[N:14]([CH3:30])[C:13]1=[O:31])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[Cl:32][C:33]1[CH:38]=[CH:37][C:36](B(O)O)=[CH:35][CH:34]=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]([OH:29])[CH2:25][CH:26]([CH3:28])[CH3:27])=[C:20]([C:36]3[CH:37]=[CH:38][C:33]([Cl:32])=[CH:34][CH:35]=3)[N:21]=[CH:22][C:15]=2[N:14]([CH3:30])[C:13]1=[O:31])([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 742994-Chlorophenylboronic acidHCID 516892Sodium BicarbonateHCID 1317370773-(3-(tert-butyldimethylsilyloxy)propyl)-6-chloro-5-(1-hydroxy-3-methylbutyl)-1-methylpyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione

Product 1

HCID 1317370783-(3-(tert-butyldimethylsilyloxy)propyl)-6-(4-chlorophenyl)-5-(1-hydroxy-3-methylbutyl)-1-methylpyrido[3,4-d]pyrimidine-2,4(1H,3H)-dioneYield 26%

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-(1-hydroxy-3-methylbutyl)-1-methylpyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione (100 mg, 0.212 mmol), 4-chlorophenyl boronic acid (66 mg, 0.424 mmol), NaHCO3 (53 mg, 1.06 mmol), aq. 2M K3PO4 (0.53 ml, 1.06 mmol) in dioxane (1 mL) and water (0.2 mL) was added Pd(dppf)Cl2 (5 mg, 0.0068 mmol). The reaction was degassed with nitrogen (3×), heated at 120° C. (MW) for 1.5 h, cooled to RT then diluted with EA (10 mL) 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-(1-hydroxy-3-methylbutyl)-1-methylpyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione (30 mg, 26% yield) as a colorless oil. LCMS: MH+ 546 and TR=2.602 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) 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-470e93c58b5e4e748f2c6d95a3801ebb
Source dataset
uspto-grants-2016_09
Patent number
US09440973B2

Reaction notes

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