Acetic Acid → n-(3-{[3-(2-Chloro-phenyl)-6-fluoro-4-oxo-3,4-dihydro-quinazolin-2-ylmethyl]-amino}-phenyl)-acetamide

HRID 1169264Notes

Reaction equation

HRID 1169264 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:17](=[O:18])[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([F:19])[CH:15]=2)[N:10]=[C:9]1C=O.[CH:22]1[CH:27]=[C:26]([NH2:28])[CH:25]=[C:24](CC(N)=O)[CH:23]=1.Cl.[CH2:34]([N:36](CC)CC)C.[C:41]([OH:44])(=O)[CH3:42].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClC(Cl)C>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:17](=[O:18])[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([F:19])[CH:15]=2)[N:10]=[C:9]1[CH2:34][NH:36][C:24]1[CH:25]=[C:26]([NH:28][C:41](=[O:44])[CH3:42])[CH:27]=[CH:22][CH:23]=1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 8471TriethylamineHCID 108822Acetamide, N-(3-aminophenyl)-, hydrochloride (1:?)HCID 5049666Sodium triacetoxyborohydrideHCID 106858093-(2-Chlorophenyl)-6-fluoro-3,4-dihydroquinazolin-4-one-2-carboxaldehyde

Product 1

HCID 10173540n-(3-{[3-(2-Chloro-phenyl)-6-fluoro-4-oxo-3,4-dihydro-quinazolin-2-ylmethyl]-amino}-phenyl)-acetamideYield 24.3%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of 3-(2-chloro-phenyl)-6-fluoro-3,4-dihydro-quinazolin-4-one-2-carboxaldehyde (0.20 g, 0.66 mmol), 3-aminoacetanilide hydrochloride (0.062 g, 0.33 mmol), triethylamine (0.092 mL, 0.66 mmol), and acetic acid (0.19 mL, 3.3 mmol) in dichloroethane (10 mL) was chilled to 0° C. and sodium triacetoxyborohydride (0.350 g, 1.65 mmol) was added. The reaction was stirred for 1 hour at 0° C. and then allowed to warm to ambient temperature and stirred 16 hours. The reaction was quenched by addition of saturated aqueous bicarbonate and continued stirring for 30 minutes. The phases were separated and the aqueous layer was extracted with methylene chloride. The combined organic phase was washed with brine, dried over magnesium sulfate and concentrated. The residue triturated with 50% isopropyl ether/hexane to afford 0.035 g (24%) of N-(3-{[3-(2-Chloro-phenyl)-6-fluoro-4-oxo-3,4-dihydro-quinazolin-2-ylmethyl]-amino}-phenyl)-acetamide as a yellow solid which had: 1H NMR δ 7.92 (dd, J=3, 8 Hz, 1H), 7.86 (dd, J=5, 9 Hz, 1H), 7.67-7.64 (m, 1H), 7.56-7.48 (m, 4H), 7.40 (dd, J=2, 7 Hz, 1H), 7.32 (d, J=7 Hz, 1H), 7.13 (s, 1H), 7.06 (t, J=8 Hz, 1H), 6.65 (d, J=8 Hz, 1H), 6.28 (d, J=8 Hz, 1H), 3.89 (ABq, Δv1-3=49 Hz, J=17 Hz, 2H), 2.12 (s, 3H); APCI MS m/z=437 (P+1).

Workup

  1. temperatureto warm to ambient temperature
  2. stirringstirred 16 hours
  3. customThe reaction was quenched by addition of saturated aqueous bicarbonate
  4. stirringcontinued stirring for 30 minutes
  5. customThe phases were separated
  6. extractionthe aqueous layer was extracted with methylene chloride
  7. washThe combined organic phase was washed with brine
  8. dry with materialdried over magnesium sulfate
  9. concentrationconcentrated
  10. customThe residue triturated with 50% isopropyl ether/hexane

Sources & evidence

ORD record
ord-f73ec43c0cd3492f85130430ded00e5d
Source dataset
uspto-grants-2003_09
Patent number
US06627755B1

Reaction notes

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