Boron tribromide → HCID 71042119, compound

HRID 925615Notes

Reaction equation

HRID 925615 reaction equation
[OH:1][C@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@@H:3]1[N:8]1[C:17](=[O:18])[C:16]2[C:11](=[C:12]3[N:31]([CH3:32])[CH2:30][CH:29]=[CH:28][C:13]3=[C:14]([CH2:19][C:20]3[CH:25]=[CH:24][C:23]([O:26]C)=[CH:22][CH:21]=3)[CH:15]=2)[N:10]=[CH:9]1.B(Br)(Br)Br>ClCCl>[OH:26][C:23]1[CH:22]=[CH:21][C:20]([CH2:19][C:14]2[CH:15]=[C:16]3[C:11](=[C:12]4[N:31]([CH3:32])[CH2:30][CH:29]=[CH:28][C:13]=24)[N:10]=[CH:9][N:8]([C@H:3]2[CH2:4][CH2:5][CH2:6][CH2:7][C@@H:2]2[OH:1])[C:17]3=[O:18])=[CH:25][CH:24]=1

Participants

4

Reactant 2

HCID 25134Boron tribromide3×HCID 71042120HCID 71042120, compound

Product 1

HCID 71042119HCID 71042119, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
-40 °C

Procedure

To a solution of 3-[(1S,2S)-2-hydroxycyclohexyl]-6-(4-methoxybenzyl)-10-methyl-9,10-dihydropyrido[3,2-h]quinazolin-4(3H)-one (0.250 g, 0.579 mmol) in 5 mL of dichloromethane at −78° C. was added boron tribromide (1 M in dichloromethane, 1.16 mL, 1.16 mmol). After 2 h, the mixture was warmed to −40° C., and additional boron tribromide was added (1 M in dichloromethane, 1.16 mL, 1.16 mmol). After 1 h, additional boron tribromide was added (1 M in dichloromethane, 1.16 mL, 1.16 mmol) and after 30 min, the reaction was quenched with methanol and concentrated in vacuo. The residue was diluted with ethyl acetate, then washed with saturated aqueous sodium bicarbonate and brine. The organic solution was dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified via silica gel chromatography, eluting with 0-5% methanol in dichloromethane, to provide the title compound that gave a proton NMR spectra consistent with theory and a mass ion (ES+) of 418.1 for [M+H]+: 1H NMR (400 MHz, CDCl3) δ 8.92 (s, 1H), 8.19 (d, J=8.5 Hz, 1H), 7.96 (s, 1H), 7.42-7.38 (m, 1H), 6.99-6.97 (m, 2H), 6.78-6.69 (m, 2H), 4.74-4.60 (m, 2H), 4.40-4.34 (m, 1H), 4.24 (s, 2H), 3.64-3.59 (m, 1H), 3.23 (s, 3H), 2.40 (br s, 1H), 2.21 (br s, 1H), 1.91-1.80 (m, 3H), 1.66-1.24 (m, 4H).

Workup

  1. waitAfter 1 h
  2. waitafter 30 min
  3. customthe reaction was quenched with methanol
  4. concentrationconcentrated in vacuo
  5. additionThe residue was diluted with ethyl acetate
  6. washwashed with saturated aqueous sodium bicarbonate and brine
  7. dry with materialThe organic solution was dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified via silica gel chromatography
  11. washeluting with 0-5% methanol in dichloromethane

Sources & evidence

ORD record
ord-61aec8d3207d4b35b4feb8bf1e49c44c
Source dataset
uspto-grants-2016_03
Patent number
US09284312B2

Reaction notes

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