Bicarbonate Ion → 3-{[3-(2-Chloro-phenyl)-6-fluoro-4-oxo-3,4-dihydro-quinazolin-2-ylmethyl]-amino}-benzonitrile

HRID 897025Notes

Reaction equation

HRID 897025 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]1[CH:20]=O.[NH2:22][C:23]1[CH:24]=[C:25]([CH:28]=[CH:29][CH:30]=1)[C:26]#[N:27].S([O-])([O-])(=O)=O.[Na+].[Na+].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-]>C(OCC)(=O)C.CCCCCC.C(O)(=O)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[CH2:20][NH:22][C:23]1[CH:24]=[C:25]([CH:28]=[CH:29][CH:30]=1)[C:26]#[N:27]

Participants

8

Reactant 5

HCID 769Bicarbonate IonHCID 167023-AminobenzonitrileHCID 24436Sodium SulfateHCID 5049666Sodium triacetoxyborohydrideHCID 106858093-(2-Chlorophenyl)-6-fluoro-3,4-dihydroquinazolin-4-one-2-carboxaldehyde

Product 1

HCID 102162253-{[3-(2-Chloro-phenyl)-6-fluoro-4-oxo-3,4-dihydro-quinazolin-2-ylmethyl]-amino}-benzonitrileYield 78.2%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 21226206Ethyl acetate hexaneSolvent

Procedure

A mixture of 3-(2-chloro-phenyl)-6-fluoro-3,4-dihydro-quinazolin-4-one-2-carboxaldehyde (0.150 g, 0.50 mmol), glacial acetic acid (10 mL), 3-aminobenzonitrile (0.050 g, 0.42 mmol), and anhydrous sodium sulfate (0.71 g, 5 mmol) was stirred at ambient temperature overnight. Tlc indicated that the imine had formed (Rf=0.43 on silica gel tic developed with 30% ethyl acetate/hexane, UV detection). Sodium triacetoxyborohydride (0.267 g, 1.26 mmol) was added and the reaction was allowed to stir over the weekend (72 hours). The mixture was poured into saturated aqueous bicarbonate and repeatedly extracted with ethyl acetate. The combined organic layer was dried over magnesium sulfate and concentrated to afford a yellow solid. This solid was triturated with 50% ethyl ether/isopropyl ether to give 0.133 g (78%) of 3-{[3-(2-chloro-phenyl)-6-fluoro-4-oxo-3,4-dihydro-quinazolin-2-ylmethyl]-amino}-benzonitrile as an off white solid which had: mp 225-228° C.; 1H NMR δ 7.93 (dd, J=3, 8 Hz, 1 H), 7.87 (dd, J=4.5, 8.5 Hz, 1 H), 7.70 (dd, J=1.5, 7.5 Hz, 1 H), 7.62-7.52 (m, 4 H), 7.40 (dd, J=1.5, 7.5 Hz, 1 H), 7.20 (t, J=8 Hz, 1 H), 6.97 (d, J=7.5 Hz, 1 H), 6.80 (dd, J=2, 8 Hz, 1 H), 6.66 (s, 1 H), 3.88 (ABq, Δv1-3=39.5 Hz, J=17 Hz, 2 H). Analysis calculated for C22H14ClFN4O.0.5 H2O: C, 63.85; H, 3.65; N, 13.54. Found: C, 63.90; H, 3.31; N, 13.46.

Workup

  1. stirringto stir over the weekend (72 hours)
  2. extractionrepeatedly extracted with ethyl acetate
  3. dry with materialThe combined organic layer was dried over magnesium sulfate
  4. concentrationconcentrated
  5. customto afford a yellow solid
  6. customThis solid was triturated with 50% ethyl ether/isopropyl ether

Sources & evidence

ORD record
ord-797f8a7cc13742688b05b4d45a97f1ea
Source dataset
uspto-grants-2005_07
Patent number
US06921764B2

Reaction notes

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