Triethylamine → Ethyl 1-cyclohexyl-7-[5-(2,4-diamino-pyrimidin-5-ylmethyl)-2,3-dimethoxy-phenylethynyl]-4-oxo-1,4-dihydro-quinoline-3-carboxylate

HRID 963393Notes

Reaction equation

HRID 963393 reaction equation
C([C:3]1[N:4]([CH:18]2[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]2)[C:5]2[C:10]([C:11](=[O:16])[C:12]=1[C:13]([OH:15])=[O:14])=[CH:9][CH:8]=[C:7](Br)[CH:6]=2)C.[C:24]([C:26]1[CH:27]=[C:28]([CH:38]=[C:39]([O:43][CH3:44])[C:40]=1[O:41][CH3:42])[CH2:29][C:30]1[C:31]([NH2:37])=[N:32][C:33]([NH2:36])=[N:34][CH:35]=1)#[CH:25].C(=O)([O-])[O-].[Na+].[Na+].[CH2:51](N(CC)CC)[CH3:52]>CN(C)C=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH:18]1([N:4]2[C:5]3[C:10](=[CH:9][CH:8]=[C:7]([C:25]#[C:24][C:26]4[CH:27]=[C:28]([CH2:29][C:30]5[C:31]([NH2:37])=[N:32][C:33]([NH2:36])=[N:34][CH:35]=5)[CH:38]=[C:39]([O:43][CH3:44])[C:40]=4[O:41][CH3:42])[CH:6]=3)[C:11](=[O:16])[C:12]([C:13]([O:15][CH2:51][CH3:52])=[O:14])=[CH:3]2)[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 10340Sodium CarbonateHCID 178909505-[3-Ethynyl-4,5-dimethoxy-benzyl]-pyrimidine-2,4-diamineHCID 19081638Ethyl 7-bromo-1-cyclohexyl-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid

Product 1

HCID 54485644Ethyl 1-cyclohexyl-7-[5-(2,4-diamino-pyrimidin-5-ylmethyl)-2,3-dimethoxy-phenylethynyl]-4-oxo-1,4-dihydro-quinoline-3-carboxylateYield 83%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
90 °C

Procedure

3 g of ethyl 7-bromo-1-cyclohexyl-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid (Example 13ad)) are dissolved in 35 ml of N,N-dimethylformamide to 90° C. under argon with 200 mg of bis(triphenylphosphine)palladium(II) dichloride and treated dropwise within one hour with a solution of 5-[3-ethynyl-4,5-dimethoxy-benzyl]-pyrimidine-2,4-diamine (Example 11b)) in 35 ml of N,N-dimethylformamide and 35 ml of triethylamine. The dark red solution is stirred at 90° C. for a further 1 hr. The reaction mixture is left to cool to room temperature and is poured into 150 ml of 10% aqueous sodium carbonate solution while stirring. After 15 min. the suspension is suction filtered and the residue is washed with 100 ml of water and then with 100 ml of diethyl ether and dried at room temperature in a high vacuum. The crude product is triturated with 50 ml of diethyl ether for one hour, filtered off under suction and dried in a high vacuum at room temperature. 3.83 g (83%) of ethyl 1-cyclohexyl-7-[5-(2,4-diamino-pyrimidin-5-ylmethyl)-2,3-dimethoxy-phenylethynyl]-4-oxo-1,4-dihydro-quinoline-3-carboxylate are obtained as a light yellow solid. M.p. 228°-230° C.

Workup

  1. waitThe reaction mixture is left
  2. temperatureto cool to room temperature
  3. stirringwhile stirring
  4. waitAfter 15 min. the suspension is
  5. filtrationsuction filtered
  6. washthe residue is washed with 100 ml of water
  7. dry with materialwith 100 ml of diethyl ether and dried at room temperature in a high vacuum
  8. customThe crude product is triturated with 50 ml of diethyl ether for one hour
  9. filtrationfiltered off under suction
  10. customdried in a high vacuum at room temperature

Sources & evidence

ORD record
ord-7be8dc74f207445ca5b343935fbf91f8
Source dataset
uspto-grants-1998_06
Patent number
US05763450

Reaction notes

Loading…