Cesium carbonate → (2,4-Dioxo-1,4-dihydro-2H-pyrido[3,4-d]pyrimidin-3-yl)-acetic acid tert-butyl ester

HRID 472764Notes

Reaction equation

HRID 472764 reaction equation
CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.[C:43]([O:47][C:48](=[O:54])[CH2:49][NH:50][C:51]([NH2:53])=[O:52])([CH3:46])([CH3:45])[CH3:44].C([O-])([O-])=O.[Cs+].[Cs+].C[O:62][C:63](=O)[C:64]1[CH:69]=[CH:68][N:67]=[CH:66][C:65]=1Br>CC([O-])=O.CC([O-])=O.[Pd+2].CCOC(C)=O.O1CCOCC1>[C:43]([O:47][C:48](=[O:54])[CH2:49][N:50]1[C:63](=[O:62])[C:64]2[CH:65]=[CH:66][N:67]=[CH:68][C:69]=2[NH:53][C:51]1=[O:52])([CH3:46])([CH3:44])[CH3:45]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 2762700Methyl 3-bromoisonicotinateHCID 86641479Ureido-acetic acid tert-butyl ester

Product 1

HCID 68591379(2,4-Dioxo-1,4-dihydro-2H-pyrido[3,4-d]pyrimidin-3-yl)-acetic acid tert-butyl ester

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

A 2-5 ml microwave vial is charged with Pd(OAc)2 (2.5 mol %, 6.6 mg, 0.0231 mmol), Xantphos (5 mol %, 27.1 mg, 0.0463 mmol), ureido-acetic acid tert-butyl ester (259 mg, 1.482 mmol), and Cs2CO3 (770.2 mg, 2.315 mmol). 3-Bromo-isonicotinic acid methyl ester (216.3 mg, 0.926 mmol) is added, followed by 1,4-dioxane (4 ml). The vessel is sealed and treated in the microwave at 120° C. for 3×3600 seconds. EtOAc is added to the reaction mixture which is then washed with brine (3×20 ml) and water (2×10 ml). The organic phase is passed through Celite® (filter material), dried (MgSO4), filtered and concentrated. The material is purified via flash column chromatography, eluting with iso-hexane:EtOAc to afford the title compound; [M+H]+ 278.

Workup

  1. customThe vessel is sealed
  2. additiontreated in the microwave at 120° C. for 3×3600 seconds
  3. washis then washed with brine (3×20 ml) and water (2×10 ml)
  4. filtrationThe organic phase is passed through Celite® (filter material)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe material is purified via flash column chromatography
  9. washeluting with iso-hexane

Sources & evidence

ORD record
ord-6da912865c7d4717b9f17b43efa37b9f
Source dataset
uspto-grants-2014_01
Patent number
US08633211B2

Reaction notes

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