Boron trifluoride etherate → HCID 22648164, compound

HRID 394091Notes

Reaction equation

HRID 394091 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[N:9]1[C:18]2[C:13](=[C:14]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=3[Cl:35])[CH:15]=[C:16]([CH:19]3[CH2:25][CH2:24][N:23]([CH2:26][CH3:27])[C:22](=O)[CH2:21][CH2:20]3)[CH:17]=2)[CH2:12][NH:11][C:10]1=[O:36].B.C1COCC1.[SiH](CC)(CC)CC.B(F)(F)F.CCOCC>C1COCC1>[Cl:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[C:3]=1[N:9]1[C:18]2[C:13](=[C:14]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=3[Cl:35])[CH:15]=[C:16]([CH:19]3[CH2:25][CH2:24][N:23]([CH2:26][CH3:27])[CH2:22][CH2:21][CH2:20]3)[CH:17]=2)[CH2:12][NH:11][C:10]1=[O:36]

Participants

6

Reactant 4

HCID 8000Boron trifluoride etherateHCID 12052TriethylsilaneHCID 2723981Borane;tetrahydrofuranHCID 22648141HCID 22648141, compound

Product 1

HCID 22648164HCID 22648164, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-(2,6-dichlorophenyl)-5-(2-chlorophenyl)-7-(1-ethyl-2-oxoazepan-5-yl)-3,4-dihydro-2(1H)-quinazolinone (EXAMPLE 78) (9.7 mg, 0.018 mmol) in THF (0.2 mL) under N2 atmosphere was added BH3.THF (88 μL, 1.0M solution in THF). The reaction was stirred at RT overnight. The solvent was removed in vacuo, and the residue was dissolved in CH2Cl2. The resulting solution was washed with brine and dried over Na2SO4. After removal of the solvent in vacuo, the residue was re-dissolved in CH2Cl2 (0.5 mL) then cooled down to 0° C. To this was added Et3SiH (3 μL, 0.036 mmol) followed by BF3.Et2O (2.5 μL, 0.04 mmol), and the mixture was slowly warmed to RT over 2 hours. It was quenched with saturated solution of NaHCO3, then extracted with CH2Cl2 three times. The combined extracts were washed with brine and dried over Na2SO4. The crude residue was purified by preparative TLC eluting with 5% 2M NH3 in MeOH(CH2Cl2 to obtain 1-(2,6-Dichlorophenyl)-5-(2-chlorophenyl)-7-(1-ethylazepan-5-yl)-3,4-dihydro-2(1H)-quinazolinone. 1H NMR (CDCl3, 500 MHz): selected data δ 1.03 (t, J=7.1 Hz, 3H), 1.6-1.87 (m, 6H), 2.52 (q, J=7.1 Hz, 2H), 2.56-2.73 (m, 5H). MS(ES) 530 (M+H); LC 1: 2.36 min.

Workup

  1. customThe solvent was removed in vacuo
  2. dissolutionthe residue was dissolved in CH2Cl2
  3. washThe resulting solution was washed with brine
  4. dry with materialdried over Na2SO4
  5. customAfter removal of the solvent in vacuo
  6. dissolutionthe residue was re-dissolved in CH2Cl2 (0.5 mL)
  7. temperaturethen cooled down to 0° C
  8. temperaturethe mixture was slowly warmed to RT over 2 hours
  9. customIt was quenched with saturated solution of NaHCO3
  10. extractionextracted with CH2Cl2 three times
  11. washThe combined extracts were washed with brine
  12. dry with materialdried over Na2SO4
  13. customThe crude residue was purified by preparative TLC
  14. washeluting with 5% 2M NH3 in MeOH(CH2Cl2

Sources & evidence

ORD record
ord-036c525cbd27471082cf3722d4198791
Source dataset
uspto-grants-2004_10
Patent number
US06809199B2

Reaction notes

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