Citric Acid → HCID 69960639, compound

HRID 840142Notes

Reaction equation

HRID 840142 reaction equation
[OH-].[K+].[NH2:3][C:4]1[C:13]2[C:8](=[CH:9][C:10]([O:22][CH3:23])=[C:11]([O:20][CH3:21])[C:12]=2[C:14]2[N:19]=[CH:18][CH:17]=[CH:16][N:15]=2)[N:7]=[C:6]([N:24]2[CH2:33][CH2:32][C:31]3[N:30]=[CH:29][CH:28]=[CH:27][C:26]=3[CH2:25]2)[CH:5]=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O.[OH-].[Na+]>CS(C)=O>[NH2:3][C:4]1[C:13]2[C:8](=[CH:9][C:10]([O:22][CH3:23])=[C:11]([O:20][CH3:21])[C:12]=2[C:14]2[N:19]=[CH:18][CH:17]=[CH:16][N:15]=2)[N:7]=[C:6]([N:24]2[CH2:33][CH2:32][C:31]3[N:30]=[CH:29][CH:28]=[CH:27][C:26]=3[CH2:25]2)[CH:5]=1

Participants

5

Reactant 3

HCID 311Citric AcidHCID 14798Sodium HydroxideHCID 70157606HCID 70157606, compound

Product 1

HCID 69960639HCID 69960639, compoundYield 17%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
95 °C

Procedure

4-Amino-6,7-dimethoxy-5-(2-pyrimidyl)-2-(5,6,7,8-tetrahydro-1,6-naphthyrid-6-yl)quinoline Potassium hydroxide powder (72 mg, 1.29 mmol) was added to a solution of the product of step (a) (530 mg, 1.28 mmol) in DMSO (5 ml). The reaction mixture was heated to 95° C. for 45 min. After cooling the reaction mixture was poured into citric acid and basified with 2N aqueous NaOH. The product was then extracted with EtOAc (×4). The combined organic layers were washed with H2O, saturated brine and dried over MgSO4. The product was purified on silica gel, eluting with CH2Cl2/MeOH/0.88NH3 (96/3.5/0.5, v/v). The product was triturated with ether to afford the title compound as an orange solid (91 mg, 17%). Rf 0.11 CH2Cl2/MeOH (95/5, v/v). MS m/z 415 (MH+) 1H NMR (CDCl3), δ: 3.10 (2H, t), 3.69 (314, s), 3.79 (2H, s), 4.00 (2H, m), 4.05 (3H, s), 4.82 (2H, s), 6.01 (1H, s), 7.05 (1H, m), 7.40 (1H, t), 7.50 (1H, m), 8.40 (1H, m), 8.90 (2H, m).

Workup

  1. temperatureAfter cooling the reaction mixture
  2. extractionThe product was then extracted with EtOAc (×4)
  3. washThe combined organic layers were washed with H2O, saturated brine
  4. dry with materialdried over MgSO4
  5. customThe product was purified on silica gel
  6. washeluting with CH2Cl2/MeOH/0.88NH3 (96/3.5/0.5
  7. customThe product was triturated with ether

Sources & evidence

ORD record
ord-420b67c97fff42adbee6f7b9ef045c37
Source dataset
uspto-grants-2002_04
Patent number
US06365599B1

Reaction notes

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