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

HRID 60163Notes

Reaction equation

HRID 60163 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].[CH:35]([C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=1B(O)O)([CH3:37])[CH3:36].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][CH:42]=[CH:43][C:38]=3[CH:35]([CH3:37])[CH3:36])[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]

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 516892Sodium BicarbonateHCID 27734772-Isopropylbenzeneboronic acidHCID 1317370763-(3-(tert-butyldimethylsilyloxy)propyl)-6-chloro-5-((4-chlorophenyl) (hydroxy)methyl)-1-methylpyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione

Product 1

HCID 1317370823-(3-(tert-butyldimethylsilyloxy)propyl)-5-((4-chlorophenyl)(hydroxy)methyl)-6-(2-isopropylphenyl)-1-methylpyrido[3,4-d]pyrimidine-2,4(1H,3H)-dioneYield 13%

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 (100 mg, 0.19 mmol), 2-isopropyl phenylboronic acid (62.52 mg, 0.38 mmol), NaHCO3 (48 mg, 0.57 mmol), aq. 2M K3PO4 (0.47 ml, 0.94 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) and water (2 mL) and filtered. 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)-5-((4-chlorophenyl)(hydroxy)methyl)-6-(2-isopropylphenyl)-1-methylpyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione (15 mg, 12.9% yield) as a colorless oil. LCMS: MH+ 608 and TR=2.668 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. filtrationfiltered
  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-38d6a579d1d941c28a513ee4e735f39c
Source dataset
uspto-grants-2016_09
Patent number
US09440973B2

Reaction notes

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