Hydrochloric Acid → HCID 22648050, compound

HRID 394220Notes

Reaction equation

HRID 394220 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:17]=[C:16]([C:18]([NH:21][C:22](=O)[CH2:23][NH:24][CH:25]([CH3:27])[CH3:26])([CH3:20])[CH3:19])[CH:15]=[C:14]2[C:9]=1[CH2:10][NH:11][C:12](=[O:37])[N:13]2[C:29]1[C:34]([Cl:35])=[CH:33][CH:32]=[CH:31][C:30]=1[Cl:36].B.C1COCC1.Cl.[OH-].[Na+]>C(OCC)(=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:17]=[C:16]([C:18]([NH:21][CH2:22][CH2:23][NH:24][CH:25]([CH3:27])[CH3:26])([CH3:19])[CH3:20])[CH:15]=[C:14]2[C:9]=1[CH2:10][NH:11][C:12](=[O:37])[N:13]2[C:29]1[C:34]([Cl:35])=[CH:33][CH:32]=[CH:31][C:30]=1[Cl:36]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 2723981Borane;tetrahydrofuranHCID 23532901HCID 23532901, compound

Product 1

HCID 22648050HCID 22648050, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

Dissolved N1-{1-[5-(2-chlorophenyl)-1-(2,6-dichlorophenyl)-2-oxo-1,2,3,4-tetrahydroquinazolin-7-yl]-1-methylethyl}-N2-isopropylglycinamide (COMPOUND DDD-4) (53 mg) borane-THF solution (3 mL of a 1M solution). The mixture was brought to and maintained at reflux for 4 h. The mixture was cooled. Aqueous 6N HCl (6 mL) was added and the mixture was heated to 80° C. for 30 min. The reaction was cooled and diluted with ethyl acetate. The aqueous layer was made basic by addition of 2N NaOH. The layers were mixed and then separated. The ethyl acetate layer was washed with aqueous 2N NaOH. The organic layer was dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The product was purified by preparative reverse phase HPLC [Waters Xterra C8 ms 19×50 mm column using a gradient elution of 90% water (+0.1% TFA)/10% CH3CN (+0.1% TFA) to 100% CH3CN (+0.1% TFA) over 12 min at 20 mL/min] giving 5-(2-chlorophenyl)-1-(2,6-dichlorophenyl)-7-(1-{[2-(isopropylamino)ethyl]amino}-1-methylethyl)-3,4-dihydroquinazolin-2(1H)-one. Mass spectrum (ESI) 545 (M+1); 547 (M+3).

Workup

  1. temperaturemaintained
  2. temperatureat reflux for 4 h
  3. temperatureThe mixture was cooled
  4. temperatureThe reaction was cooled
  5. additionThe layers were mixed
  6. customseparated
  7. washThe ethyl acetate layer was washed with aqueous 2N NaOH
  8. dry with materialThe organic layer was dried over anhydrous Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe product was purified by preparative reverse phase HPLC [Waters Xterra C8 ms 19×50 mm column
  12. washa gradient elution of 90% water (+0.1% TFA)/10% CH3CN (+0.1% TFA) to 100% CH3CN (+0.1% TFA) over 12 min at 20 mL/min]

Sources & evidence

ORD record
ord-e66ea67ca13c4ed99564e6a3575977c2
Source dataset
uspto-grants-2004_10
Patent number
US06809199B2

Reaction notes

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