Ethanol → HCID 69710392, compound

HRID 392098Notes

Reaction equation

HRID 392098 reaction equation
Cl[C:2]1[C:3]2[CH2:13][N:12]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:11][CH2:10][C:4]=2[N:5]=[C:6]([S:8][CH3:9])[N:7]=1.[Cl:21][C:22]1[CH:27]=[C:26]([Cl:28])[CH:25]=[CH:24][C:23]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+].C(O)C>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].C1(P(C2C=CC=CC=2)CCCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O>[Cl:21][C:22]1[CH:27]=[C:26]([Cl:28])[CH:25]=[CH:24][C:23]=1[C:2]1[C:3]2[CH2:13][N:12]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:11][CH2:10][C:4]=2[N:5]=[C:6]([S:8][CH3:9])[N:7]=1

Participants

9

Reactant 4

HCID 702EthanolHCID 10340Sodium CarbonateHCID 2734659(2,4-Dichlorophenyl)boronic acidHCID 86583989HCID 86583989, compound

Product 1

HCID 69710392HCID 69710392, compoundYield 104.2%

Reagents, catalysts & solvents 4

HCID 821241,4-Bis(diphenylphosphino)butaneCatalystHCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

A mixture of tert-butyl 4-chloro-2-methylthio-5,6,7,8-tetrahydropyridino[4,3-d]pyrimidine-6-carboxylate (334 mg, 1.06 mmol), 2,4-dichlorobenzeneboronic acid (222 mg, 1.16 mmol), bis(dibenzylideneacetone)palladium(0) (48 mg, 0.053 mmol) and 1,4-bis(diphenylphosphino)butane (45 mg, 0.11 mmol) in toluene (2 ml), aqueous 1M sodium carbonate solution (1 ml) and ethanol (0.5 ml) was heated under reflux for 19 h under nitrogen. The reaction mixture was then cooled, water was added, and the toluene layer was separated. The aqueous layer was extracted with ethyl acetate and the combined organic extracts were dried (MgSO4), filtered, and the filtrate concentrated in vacuo. The crude product was purified by column chromatography using 15% acetone in hexanes as eluent, giving tert-butyl 4-(2,4-dichlorophenyl)-2-methylthio-5,6,7,8-tetrahydropyridino[4,3-d]pyrimidine-6-carboxylate (471 mg, yield>100%) as a light yellow sticky foam.

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 19 h under nitrogen
  3. temperatureThe reaction mixture was then cooled
  4. customthe toluene layer was separated
  5. extractionThe aqueous layer was extracted with ethyl acetate
  6. dry with materialthe combined organic extracts were dried (MgSO4)
  7. filtrationfiltered
  8. concentrationthe filtrate concentrated in vacuo
  9. customThe crude product was purified by column chromatography

Sources & evidence

ORD record
ord-c345b5b078034748a51d240ff67ceb40
Source dataset
uspto-grants-2004_10
Patent number
US06800632B2

Reaction notes

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