Aniline → (S)-tert-butyl 1-(5-chloro-4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)ethylcarbamate

HRID 1474070Notes

Reaction equation

HRID 1474070 reaction equation
P(=O)(OC1C=CC=CC=1)OC1C=CC=CC=1.[NH2:17][C:18]1[CH:26]=[CH:25][CH:24]=[C:23]([Cl:27])[C:19]=1[C:20]([OH:22])=O.[C:28]([O:32][C:33]([NH:35][C@@H:36]([CH3:40])[C:37](O)=O)=[O:34])([CH3:31])([CH3:30])[CH3:29].[NH2:41][C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1>N1C=CC=CC=1.CCOC(C)=O>[Cl:27][C:23]1[CH:24]=[CH:25][CH:26]=[C:18]2[C:19]=1[C:20](=[O:22])[N:41]([C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)[C:37]([C@@H:36]([NH:35][C:33](=[O:34])[O:32][C:28]([CH3:31])([CH3:30])[CH3:29])[CH3:40])=[N:17]2

Participants

7

Reactant 4

HCID 6115AnilineHCID 62550Diphenyl phosphiteHCID 750712-Amino-6-chlorobenzoic acidHCID 85082Tert-butoxycarbonylalanine

Product 1

HCID 86686186(S)-tert-butyl 1-(5-chloro-4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)ethylcarbamate

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
40 °C

Procedure

Diphenyl phosphonate (1.9 mL, 10 mmol) was added to a solution of 2-amino-6-chlorobenzoic acid (495 mg, 2.9 mmol) and (S)-2-(tert-butoxycarbonylamino)propanoic acid (710 mg, 3.77 mmol) in pyridine (3 mL). The reaction mixture was stirred at 40° C. for 2 hours. Aniline (274 mg, 3.48 mmol) was then added to the reaction mixture, which was then stirred at 55° C. for 12 hours. The reaction mixture was cooled to room temperature. This mixture was then diluted with EtOAc (50 mL), washed with 1N aqueous HCl (2×50 mL), brine (50 mL), and dried over sodium sulfate. The organics layer was filtered and concentrated in vacuuo to afford material which was purified by column chromatography on SiO2 eluting with EtOAc in hexanes (0-50%) to afford (S)-tert-butyl 1-(5-chloro-4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)ethylcarbamate as a solid. ES/MS m/z=400.1 (M+H)+.

Workup

  1. stirringwas then stirred at 55° C. for 12 hours
  2. temperatureThe reaction mixture was cooled to room temperature
  3. washwashed with 1N aqueous HCl (2×50 mL), brine (50 mL)
  4. dry with materialdried over sodium sulfate
  5. filtrationThe organics layer was filtered
  6. concentrationconcentrated in vacuuo
  7. customto afford material which
  8. customwas purified by column chromatography on SiO2 eluting with EtOAc in hexanes (0-50%)

Sources & evidence

ORD record
ord-2bfc5a8cce6840a2a5382504645311fc
Source dataset
uspto-grants-2015_04
Patent number
US09018221B2

Reaction notes

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