2-Aminopyrimidine → HCID 58044075, compound

HRID 1918897Notes

Reaction equation

HRID 1918897 reaction equation
N[C:2]1[N:7]=[CH:6][CH:5]=[CH:4][N:3]=1.Br[C:9]1[C:10](=[O:16])[NH:11][CH:12]=[C:13]([Br:15])[CH:14]=1.C[Si](C)(C)[N-:19][Si](C)(C)C.[Li+].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(OCC)(=O)C.O.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].O1CCOCC1.C1COCC1>[Br:15][C:13]1[CH:14]=[C:9]([NH:19][C:6]2[CH:5]=[CH:4][N:3]=[CH:2][N:7]=2)[C:10](=[O:16])[NH:11][CH:12]=1

Participants

10

Reactant 4

HCID 79782-AminopyrimidineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 6428263,5-Dibromo-2-hydroxypyridineHCID 2733832Lithium Hexamethyldisilazide

Product 1

HCID 58044075HCID 58044075, compoundYield 24%

Reagents, catalysts & solvents 5

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

A 250-mL three-neck round-bottomed flask equipped with a reflux condenser, magnetic stirrer and nitrogen inlet was charged with 2-aminopyrimidine (376 mg, 3.95 mmol), 3,5-dibromo pyridin-2(1H)-one (1.00 g, 3.95 mmol), 1 M THF solution of lithium hexamethyldisilazide (20 mL, 20.0 mmol), and 1,4-dioxane (25 mL). After bubbling nitrogen through the resulting suspension for 30 min, Xantphos (194 mg, 0.211 mmol) and tris(dibenzylideneacetone)dipalladium(0) (165 mg, 0.197 mmol) were added, and the reaction mixture was heated at reflux for 3 h. After this time, the mixture was cooled to room temperature and diluted with ethyl acetate (150 mL) and water (30 mL). The organic layer was separated, and the aqueous layer was extracted with ethyl acetate (3×150 mL). The combined organic extracts were dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by flash chromatography followed by trituration with ethyl acetate (20 mL) to afford a 24% yield (250 mg) of 154a as an off-white solid: mp 150-151° C.; 1H NMR (500 MHz, DMSO-d6) d 12.03 (s, 1H), 9.27 (s, 1H), 8.54 (s, 1H), 8.20 (d, 1H, J=6.0 Hz), 7.85 (s, 1H), 6.64 (d, 1H, J=6.0 Hz); MS (ESI+) m/z 268.2 (M+H).

Workup

  1. customA 250-mL three-neck round-bottomed flask equipped with a reflux condenser, magnetic stirrer and nitrogen inlet
  2. customAfter bubbling nitrogen through the resulting suspension for 30 min
  3. temperaturethe reaction mixture was heated
  4. temperatureat reflux for 3 h
  5. customThe organic layer was separated
  6. extractionthe aqueous layer was extracted with ethyl acetate (3×150 mL)
  7. dry with materialThe combined organic extracts were dried over sodium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-56f56aac68094c87ade140e8da4f65a6
Source dataset
uspto-grants-2013_12
Patent number
US08618107B2

Reaction notes

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