Dichloromethane → 6-(3',4'-dichloro-biphenyl-2-ylmethyl)-9-hydroxy-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione

HRID 2169211Notes

Reaction equation

HRID 2169211 reaction equation
C([O:8][C:9]1[C:14](=[O:15])[N:13]=[C:12]([CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2Br)[N:11]2[CH2:24][CH2:25][N:26]([CH:29]([CH3:31])[CH3:30])[C:27](=[O:28])[C:10]=12)C1C=CC=CC=1.[Cl:32][C:33]1[CH:34]=[C:35](B(O)O)[CH:36]=[CH:37][C:38]=1[Cl:39].C([O-])([O-])=O.[Na+].[Na+].ClCCl>CO.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:32][C:33]1[CH:34]=[C:35]([C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=2[CH2:16][C:12]2[N:11]3[CH2:24][CH2:25][N:26]([CH:29]([CH3:30])[CH3:31])[C:27](=[O:28])[C:10]3=[C:9]([OH:8])[C:14](=[O:15])[N:13]=2)[CH:36]=[CH:37][C:38]=1[Cl:39]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 27343303,4-Dichlorobenzeneboronic acidHCID 867258609-benzyloxy-6-(2-bromobenzyl)-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione

Product 1

HCID 867258616-(3',4'-dichloro-biphenyl-2-ylmethyl)-9-hydroxy-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dioneYield 15.2%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolvent

Procedure

9-Benzyloxy-6-(2-bromobenzyl)-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione (71) (0.1 g, 207 μmol, Eq: 1.00, ˜40% pure), 3,4-dichlorophenylboronic acid (47.5 mg, 249 μmol, Eq: 1.2), Na2CO3 (65.9 mg, 622 μmol, Eq: 3) and tetrakis(triphenylphosphine)palladium (0) (24.0 mg, 20.7 μmol, Eq: 0.1) were stirred in methanol (0.9 ml)/dichloromethane (300 μl) in the microwave at 115° C. for 30 minutes. The reaction mixture stood at room temperature overnight. The supernatant was pipetted off, concentrated and purified by SiO2 flash chromatography (4 g SiO2, dichloromethane/methanol 0-5% methanol) to afford 6-(3′,4′-dichloro-biphenyl-2-ylmethyl)-9-hydroxy-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione (72) (0.016 g, 31.4 μmol, 15.2% yield, 90% pure) as a light yellow solid.

Workup

  1. concentrationconcentrated
  2. custompurified by SiO2 flash chromatography (4 g SiO2, dichloromethane/methanol 0-5% methanol)

Sources & evidence

ORD record
ord-ebb65bc18e0e46258097fd454f99966f
Source dataset
uspto-grants-2015_06
Patent number
US09045486B2

Reaction notes

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