Potassium Phosphate, Tribasic → HCID 131737086, compound

HRID 60171Notes

Reaction equation

HRID 60171 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:34]=[C:35](B(O)O)[CH:36]=[CH:37][CH:38]=1.[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]([CH3:27])[CH3:28])=[C:20]([C:37]3[CH:36]=[CH:35][CH:34]=[C:33]([Cl:32])[CH:38]=3)[N:21]=[CH:22][C:15]=2[N:14]([CH3:30])[C:13]1=[O:31])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:2])[CH3:3]

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 2734323(3-Chlorophenyl)boronic acidHCID 1317370773-(3-(tert-butyldimethylsilyloxy)propyl)-6-chloro-5-(1-hydroxy-3-methylbutyl)-1-methylpyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione2×

Product 1

HCID 131737086HCID 131737086, compoundYield 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 (See Compound 48, step 1, 100 mg, 0.212 mmol), 3-chlorophenyl boronic acid (66 mg, 0.424 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, diluted with EA (2 mL) and water (2 mL) then filtered through Celite. The filtrate was concentrated to a residue which was purified by Prep TLC PE/EA (2:1) to give 3-(3-(tert-butyldimethylsilyloxy)propyl)-6-(3-chlorophenyl)-5-(1-hydroxy-3-methylbutyl)-1-methylpyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione (30 mg, 26% yield) as colorless oil. LCMS: MH+ 546 and TR=2.569 min.

Workup

  1. customThe reaction was degassed with nitrogen (3×)
  2. temperatureheated at 120° C. (MW) for 1.5 h
  3. additiondiluted with EA (2 mL) and water (2 mL)
  4. filtrationthen filtered through Celite
  5. concentrationThe filtrate was concentrated to a residue which
  6. customwas purified by Prep TLC PE/EA (2:1)

Sources & evidence

ORD record
ord-49d1345ef44e45fb8b2f16bc74723453
Source dataset
uspto-grants-2016_09
Patent number
US09440973B2

Reaction notes

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