Hydrochloric Acid → HCID 178520493, compound

HRID 2185194Notes

Reaction equation

HRID 2185194 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[N:19]=[C:18]([OH:20])[C:17]3[C:12](=[C:13]([CH2:24][CH2:25][C:26]([OH:28])=O)[CH:14]=[C:15]([N+:21]([O-:23])=[O:22])[CH:16]=3)[N:11]=2)[CH:5]=[CH:6][C:7]=1[Cl:8].COC(=O)CCC1C=C([N+]([O-])=O)C=C2C=1N=C(Cl)N=C2O.Cl[C:51]1[CH:52]=[C:53]([CH:55]=[CH:56][C:57]=1[Cl:58])[NH2:54].[OH-].[Li+].Cl>CN1CCCC1=O.O1CCCC1.O>[Cl:58][C:57]1[CH:56]=[CH:55][C:53]([NH:54][C:26](=[O:28])[CH2:25][CH2:24][C:13]2[CH:14]=[C:15]([N+:21]([O-:23])=[O:22])[CH:16]=[C:17]3[C:12]=2[N:11]=[C:10]([NH:9][C:4]2[CH:5]=[CH:6][C:7]([Cl:8])=[C:2]([Cl:1])[CH:3]=2)[N:19]=[C:18]3[OH:20])=[CH:52][CH:51]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 72573,4-DichloroanilineHCID 178499996HCID 178499996, compoundHCID 178525334HCID 178525334, compound

Product 1

HCID 178520493HCID 178520493, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
125 °C

Procedure

3-[2-(3,4-Dichlorophenylamino)-4-hydroxy-6-nitro-quinazolin-8-yl]propionicacid. To a solution of 3-(2-chloro-4-hydroxy-6-nitroquinazolin-8-yl)propionic acid methyl ester (0.536 g) in 1-methyl-2-pyrrolidinone (10 mL) was added 3,4-dichloroaniline (0.890 g). The reaction mixture was heated to 125° C. for 6 h, then cooled to room temperature and stirred for 48 h. The solvent was removed in vacuo and the residue was diluted with water (20 mL). The precipitate that formed was collected via filtration, washed with water and dried to give a brown solid which was dissolved in tetrahydrofuran (30 mL) and water (30 mL). To this solution was added lithium hydroxide (0.507 g) and the resulting mixture was stirred at room temperature for 17 h. The pH of the solution was adjusted to ca. 3 using 1.2 M hydrochloric acid and the solvent was removed in vacuo. The residue was triturated with water and dried to afford the title compound as a solid (0.744 g). 1H NMR (300 MHz, DMSO-d6): 12.20 (s, 1H), 11.58 (s, 1H), 9.85 (s, 1H), 8.58 (d, J=2.8 Hz, 1H), 8.34 (d, J=2.8 Hz, 1H), 8.24 (D, J=2.8 Hz, 1H), 7.67-6.55 (m, 2H), 3.18 (t, J=7.5 Hz, 2H), 2.67 (t, J=7.3 Hz, 2H); HPLC (Method D): 7.68 min; MS (ES−): m/z 421.

Workup

  1. temperaturecooled to room temperature
  2. customThe solvent was removed in vacuo
  3. additionthe residue was diluted with water (20 mL)
  4. customThe precipitate that formed
  5. filtrationwas collected via filtration
  6. washwashed with water
  7. customdried
  8. customto give a brown solid which
  9. stirringthe resulting mixture was stirred at room temperature for 17 h
  10. customthe solvent was removed in vacuo
  11. customThe residue was triturated with water
  12. customdried

Sources & evidence

ORD record
ord-bdea3b9db8484c54a084ec2bf76a4608
Source dataset
uspto-grants-2002_06
Patent number
US06399603B1

Reaction notes

Loading…