4-Aminopyrimidine → HCID 118598941, compound

HRID 1050325Notes

Reaction equation

HRID 1050325 reaction equation
Cl[C:2]1[C:21](=[O:22])[N:6]2[CH2:7][CH2:8][N:9]([CH2:12][C:13]3[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=3)[C:10](=[O:11])[C:5]2=[CH:4][CH:3]=1.[N:23]1[CH:28]=[CH:27][C:26]([NH2:29])=[N:25][CH:24]=1.CC(C)([O-])C.[Na+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>O1CCOCC1.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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:20][O:19][C:16]1[CH:17]=[CH:18][C:13]([CH2:12][N:9]2[CH2:8][CH2:7][N:6]3[C:21](=[O:22])[C:2]([NH:29][C:26]4[CH:27]=[CH:28][N:23]=[CH:24][N:25]=4)=[CH:3][CH:4]=[C:5]3[C:10]2=[O:11])=[CH:14][CH:15]=1

Participants

7

Reactant 4

HCID 689584-AminopyrimidineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxideHCID 118598864HCID 118598864, compound

Product 1

HCID 118598941HCID 118598941, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of 7-chloro-2-(4-methoxybenzyl)-3,4-dihydro-1H-pyrido[1,2-a]pyrazine-1,6-(2H)-dione (3, 0.45 g, 1.41 mmol) in dioxane (10 mL), pyrimidin-4-amine (4, 0.13 g, 1.41 mmol), sodium tert-butoxide (0.41 g, 4.2 mmol) followed by X-Phos (0.14 g, 0.28 mmol) were added and the reaction mixture was degassed with argon for 5 min. Tris(dibenzylideneacetone)dipalladium(0) (0.13 g, 0.14 mmol) was added and the reaction mixture was degassed with argon for another 5 min and stirred at 110° C. for 16 h. The reaction mixture was diluted with water and the compound was extracted in ethyl acetate. The organic layer was washed with brine, separated, dried over sodium sulphate and concentrated under reduced pressure. The residue obtained was purified via column chromatography (silica, methanol/dichloromethane=5%) to afford 2-(4-methoxybenzyl)-7-(pyrimidin-4-ylamino)-3,4-dihydro-1H-pyrido[1,2-c]pyrazine-1,6(2H)-dione (5) as a yellow solid. Yield: 0.42 g, 79%; MS (ESI) m/z 378 [M+1]+.

Workup

  1. additionwere added
  2. customthe reaction mixture was degassed with argon for 5 min
  3. customthe reaction mixture was degassed with argon for another 5 min
  4. additionThe reaction mixture was diluted with water
  5. extractionthe compound was extracted in ethyl acetate
  6. washThe organic layer was washed with brine
  7. customseparated
  8. dry with materialdried over sodium sulphate
  9. concentrationconcentrated under reduced pressure
  10. customThe residue obtained
  11. customwas purified via column chromatography (silica, methanol/dichloromethane=5%)

Sources & evidence

ORD record
ord-25e9ede39a88457ebb6b290b831a2aca
Source dataset
uspto-grants-2016_07
Patent number
US09382248B2

Reaction notes

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