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

HRID 472760Notes

Reaction equation

HRID 472760 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+].I[C:62]1[C:63]([C:68](OC)=[O:69])=[N:64][CH:65]=[CH:66][CH:67]=1>CCOC(C)=O.CC([O-])=O.CC([O-])=O.[Pd+2].O1CCOCC1>[C:43]([O:47][C:48](=[O:54])[CH2:49][N:50]1[C:68](=[O:69])[C:63]2[N:64]=[CH:65][CH:66]=[CH:67][C:62]=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 819397Methyl 3-iodopyridine-2-carboxylateHCID 86641479Ureido-acetic acid tert-butyl ester

Product 1

HCID 68591435(2,4-Dioxo-1,4-dihydro-2H-pyrido[3,2-d]pyrimidin-3-yl)-acetic acid t-butyl ester

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 8857Ethyl AcetateSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

A 2-5 ml Biotage microwave vial is charged with Pd(OAc)2 (2.5 mol %, 4.6 mg, 0.019 mmol), Xantphos (5 mol %, 22.3 mg, 0.038 mmol), ureido-acetic acid tert-butyl ester (223.7 mg, 1.216 mmol), and Cs2CO3 (736.6 mg, 1.9 mmol). Methyl 3-iodopyridine-2-carboxylate (200.4 mg, 0.76 mmol) is added, followed by 1-4-dioxane (4 ml). The vessel is sealed and treated in the microwave at 120° C. for 5400 seconds. EtOAc was added to the mixture and decanted off. LCMS of this (+ELS) indicated no product. Water added to the residue giving rise to a white solid. LCMS of this material (+ELS) showed product. Material taken up in EtOAc, washed with brine (3×20 ml), then water (2×20 ml). The organic portions are passed through Celite® and the solvent removed in vacuo to give the title compound; [M+H]+ 278

Workup

  1. customThe vessel is sealed
  2. additiontreated in the microwave at 120° C. for 5400 seconds
  3. customdecanted off
  4. additionWater added to the residue
  5. customgiving rise to a white solid
  6. washwashed with brine (3×20 ml)
  7. customthe solvent removed in vacuo

Sources & evidence

ORD record
ord-4ac086dc38f8418b9d811bba890c773f
Source dataset
uspto-grants-2014_01
Patent number
US08633211B2

Reaction notes

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