1,8-Diazabicyclo(5.4.0)undec-7-ene → HCID 54545751, compound

HRID 1264225Notes

Reaction equation

HRID 1264225 reaction equation
C(OC(=O)[NH:7][C:8]1[C:13](I)=[CH:12][N:11]=[CH:10][N:9]=1)(C)(C)C.[CH3:16][O:17][C:18](=[O:27])[C:19]1[CH:24]=[CH:23][C:22]([C:25]#[CH:26])=[CH:21][CH:20]=1.N12CCCN=C1CCCCC2>CN(C=O)C.C(OCC)(=O)C.[Cu](I)I.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl>[CH3:16][O:17][C:18](=[O:27])[C:19]1[CH:24]=[CH:23][C:22]([C:25]2[NH:7][C:8]3[N:9]=[CH:10][N:11]=[CH:12][C:13]=3[CH:26]=2)=[CH:21][CH:20]=1

Participants

8

Reactant 3

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 640163Methyl 4-ethynylbenzoateHCID 70025342HCID 70025342, compound

Product 1

HCID 54545751HCID 54545751, compoundYield 52.7%

Reagents, catalysts & solvents 4

HCID 83717Copper iodideCatalystHCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of (5-iodo-pyrimidin-4-yl)carbamic acid tert-butyl ester (1.46 g, 4.55 mmol) (reference example 44a) in DMF (15 mL) is added 4-ethynyl-benzoic acid methyl ester (0.721 g, 4.5 mmol)(reference example 46), copper iodide 99.999% (21 mg, 0.112 mmol), bis(triphenylphosphine)palladium(II)chloride (158 mg, 0.225 mmol) and 1,8-diazabicyclo[5.4.0]undec-7-ene (1.5 mL, 10 mmol). The resulting solution is heated to 100° C. and stirred for 1 hour then cooled to 20° C. The solution is diluted with ethyl acetate, washed with water and brine, dried over MgSO4 and concentrated. The residue is purified by flash chromatography (eluting with 50% ethyl acetate, 5% methanol in hexanes) to give 601 mg of title compound as a yellow crystalline solid. 1H NMR (DMSO) δ 3.89 (s, 3H), 7.24 (s, 1H), 8.06 (d, J=8 Hz, 2H), 8.14 (d, J=8 Hz, 2H), 8.81 (bs, 1H), 9.05 (bs, 1H), 12.79 (bs, 1H). MS (ion spray) m/z 254 (M+H)+.

Workup

  1. temperaturethen cooled to 20° C
  2. washwashed with water and brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated
  5. customThe residue is purified by flash chromatography (eluting with 50% ethyl acetate, 5% methanol in hexanes)

Sources & evidence

ORD record
ord-8c7cc12631ba4d7aa5b866d91ec1e779
Source dataset
uspto-grants-2003_04
Patent number
US06541505B1

Reaction notes

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