Diisopropylethylamine → 5-(2-chlorophenyl)-1-(2,6-dichlorophenyl)-7-[(5-isopropyl-2,5-diazabicyclo[2.2.1]hept-2-yl)sulfonyl]-3-(4-methoxybenzyl)-3,4-dihydroquinazolin-2(1H)-one

HRID 394200Notes

Reaction equation

HRID 394200 reaction equation
[CH:1]([N:4]1[CH2:9][CH:8]2[CH2:10][CH:5]1[CH2:6][NH:7]2)([CH3:3])[CH3:2].C(N(C(C)C)CC)(C)C.[Cl:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[C:27]1[CH:36]=[C:35]([S:37](Cl)(=[O:39])=[O:38])[CH:34]=[C:33]2[C:28]=1[CH2:29][N:30]([CH2:50][C:51]1[CH:56]=[CH:55][C:54]([O:57][CH3:58])=[CH:53][CH:52]=1)[C:31](=[O:49])[N:32]2[C:41]1[C:46]([Cl:47])=[CH:45][CH:44]=[CH:43][C:42]=1[Cl:48]>C1COCC1>[Cl:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[C:27]1[CH:36]=[C:35]([S:37]([N:7]2[CH2:6][CH:5]3[CH2:10][CH:8]2[CH2:9][N:4]3[CH:1]([CH3:3])[CH3:2])(=[O:39])=[O:38])[CH:34]=[C:33]2[C:28]=1[CH2:29][N:30]([CH2:50][C:51]1[CH:52]=[CH:53][C:54]([O:57][CH3:58])=[CH:55][CH:56]=1)[C:31](=[O:49])[N:32]2[C:41]1[C:42]([Cl:48])=[CH:43][CH:44]=[CH:45][C:46]=1[Cl:47]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 226479002-Isopropyl-2,5-diazabicyclo[2.2.1]heptaneHCID 226481005-(2-Chlorophenyl)-1-(2,6-dichlorophenyl)-3-(4-methoxybenzyl)-2-oxo-1,2,3,4-tetrahydroquinazoline-7-sulfonyl chloride

Product 1

HCID 226480675-(2-chlorophenyl)-1-(2,6-dichlorophenyl)-7-[(5-isopropyl-2,5-diazabicyclo[2.2.1]hept-2-yl)sulfonyl]-3-(4-methoxybenzyl)-3,4-dihydroquinazolin-2(1H)-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2-isopropyl-2,5-diazabicyclo[2.2.1]heptane (INTERMEDIATE ABA2) (35 μL, ca. 0.249 mmol) and diisopropylethylamine (32 mg, 0.249 mmol) were added to a mixture of 5-(2-chlorophenyl)-1-(2,6-dichlorophenyl)-3-(4-methoxybenzyl)-2-oxo-1,2,3,4-tetrahydroquinazoline-7-sulfonyl chloride (103 mg, 0.166 mmol) (COMPOUND CCC8) in 2 mL THF at 0° C. The mixture was warmed to rt, stirred at this temperature for 0.5 h, and concentrated under reduced pressure. The residue was diluted with ethyl acetate and added to 6 mL of 1M aqueous HCl The phases were separated and the aqueous was extracted with 3×15 mL of ethyl acetate. The combined organic layers were washed with brine, dried (Na2SO4), and concentrated under reduced pressure. The product was purified by preparative thin-layer chromatography, eluting with 93:7 CH2Cl2-methanol to yield the 5-(2-chlorophenyl)-1-(2,6-dichlorophenyl)-7-[(5-isopropyl-2,5-diazabicyclo[2.2.1]hept-2-yl)sulfonyl]-3-(4-methoxybenzyl)-3,4-dihydroquinazolin-2(1H)-one. Mass spectrum (ESI) 725 (M+1).

Workup

  1. concentrationconcentrated under reduced pressure
  2. additionThe residue was diluted with ethyl acetate
  3. additionadded to 6 mL of 1M aqueous HCl The phases
  4. customwere separated
  5. extractionthe aqueous was extracted with 3×15 mL of ethyl acetate
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated under reduced pressure
  9. customThe product was purified by preparative thin-layer chromatography
  10. washeluting with 93:7 CH2Cl2-methanol

Sources & evidence

ORD record
ord-42bef7ef593c498a83b30189cb8db461
Source dataset
uspto-grants-2004_10
Patent number
US06809199B2

Reaction notes

Loading…