Potassium Carbonate → 2-Amino-8-ethyl-4-methyl-6-(4-methyl-3-thienyl)pyrido[2,3-d]pyrimidin-7(8H)-one

HRID 1893908Notes

Reaction equation

HRID 1893908 reaction equation
O1CCOCC1.[NH2:7][C:8]1[N:9]=[C:10]([CH3:22])[C:11]2[CH:17]=[C:16](Br)[C:15](=[O:19])[N:14]([CH2:20][CH3:21])[C:12]=2[N:13]=1.[CH3:23][C:24]1[C:25](B(O)O)=[CH:26][S:27][CH:28]=1.C([O-])([O-])=O.[K+].[K+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[NH2:7][C:8]1[N:9]=[C:10]([CH3:22])[C:11]2[CH:17]=[C:16]([C:25]3[C:24]([CH3:23])=[CH:28][S:27][CH:26]=3)[C:15](=[O:19])[N:14]([CH2:20][CH3:21])[C:12]=2[N:13]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 50839314-Methyl-3-thiopheneboronic acidHCID 576069632-amino-6-bromo-8-ethyl-4-methylpyrido[2,3-d]pyrimidin-7(8H)-one

Product 1

HCID 161230642-Amino-8-ethyl-4-methyl-6-(4-methyl-3-thienyl)pyrido[2,3-d]pyrimidin-7(8H)-oneYield 55%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A 3:1 solution of dioxane and water (4 mL) was added to a flask charged with 2-amino-6-bromo-8-ethyl-4-methylpyrido[2,3-d]pyrimidin-7(8H)-one (0.140 g, 0.495 mmol) from above, 4-methylthiophene-3-boronic acid (0.140 g, 0.989 mmol), Pd(PPh3)4 (0.057 mg, 0.050 mmol), and K2CO3 (0.205 g, 1.48 mmol). The flask was flushed with nitrogen and fitted with a reflux condenser and heated to 100° C. After 12 hours the reaction was cooled to room temperature and diluted with ethyl acetate (70 mL) and washed with water. The aqueous phase was separated and washed with an additional amount of ethyl acetate (70 mL). The organic phases were combined and washed with brine, separated and dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified on SiO2 (1:1 methylene chloride:ethyl acetate) to give 2-Amino-8-ethyl-4-methyl-6-(4-methyl-3-thienyl)pyrido[2,3-d]pyrimidin-7(8H)-one (0.081 g, 55% yield) as an off-white solid: 1H NMR (400 MHz, DMSO-d6): δ 7.84 (s, 1H), 7.46 (d, J=4.0 Hz, 1H), 7.19 (m, 3H), 4.32 (q, J=8.0 Hz, 2H), 2.52 (s, 3H), 2.11 (bs, 3H), 1.19 (t, J=8.0 Hz, 3H); MS (EI) for C15H16N4OS: 301.1 (MH+).

Workup

  1. customThe flask was flushed with nitrogen
  2. customfitted with a reflux condenser
  3. temperatureAfter 12 hours the reaction was cooled to room temperature
  4. additiondiluted with ethyl acetate (70 mL)
  5. washwashed with water
  6. customThe aqueous phase was separated
  7. washwashed with an additional amount of ethyl acetate (70 mL)
  8. washwashed with brine
  9. customseparated
  10. dry with materialdried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customThe residue was purified on SiO2 (1:1 methylene chloride:ethyl acetate)

Sources & evidence

ORD record
ord-53d911e72c3d4d21a1a4d796fcae6979
Source dataset
uspto-grants-2013_08
Patent number
US08513266B2

Reaction notes

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