HomeMCPWorkbenchSkills
HomeWorkbenchNotificationsMe
llms.txt · MCP GuidePrivacy Policy · Terms of Service · Supportv1.8.0
  1. Home
  2. /Reaction

p-Toluenesulfonic acid → 8-Chloro-3-{3-[5-(4-fluoro-phenyl)-2,5-diaza-bicyclo[2.2.2]oct-2-yl]-propyl}-1H-quinazoline-2,4-dione

HRID 1266993
Notes
Print preview

Reaction equation

HRID 1266993 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:15]=1[N:14]=[C:13]1[N:8]([CH2:9][CH2:10][CH2:11][O:12]1)[C:7]2=[O:16].[F:17][C:18]1[CH:23]=[CH:22][C:21]([N:24]2[CH2:29][CH:28]3[CH2:30][CH2:31][CH:25]2[CH2:26][NH:27]3)=[CH:20][CH:19]=1.C(N(CC)CC)C.C1(C)C=CC(S(O)(=O)=O)=CC=1>CC(N(C)C)=O.O>[Cl:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:15]=1[NH:14][C:13](=[O:12])[N:8]([CH2:9][CH2:10][CH2:11][N:27]1[CH2:26][CH:25]3[CH2:31][CH2:30][CH:28]1[CH2:29][N:24]3[C:21]1[CH:22]=[CH:23][C:18]([F:17])=[CH:19][CH:20]=1)[C:7]2=[O:16]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 8471TriethylamineHCID 114590268-chloro-3,4-dihydro-2H-1-oxa-4a,9-diaza-anthracen-10-oneHCID 120525482-(4-Fluorophenyl)-2,5-diazabicyclo[2.2.2]octane

Product 1

HCID 101143138-Chloro-3-{3-[5-(4-fluoro-phenyl)-2,5-diaza-bicyclo[2.2.2]oct-2-yl]-propyl}-1H-quinazoline-2,4-dioneYield 32.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
120 °C

Procedure

8-Chloro-3,4-dihydro-2H-1-oxa-4a,9-diaza-anthracen-10-one (0.35, 1.49 mmol), 2-(4-Fluoro-phenyl)-2,5-diaza-bicyclo[2.2.2]octane (HCl salt) (0.30g, 1.24 mmol), triethylamine (0.21 ml, 1.49 mmol), p-toluene sulfonic acid (0.036 g, 0.187 mmol) were combined in dimethyl acetamide (2 ml) and heated at 120° C. for 15 hours. The reaction was cooled to room temperature, diluted with H2O (200 mL) and extracted with ethyl acetate (3×100 mL). The pooled organic layers were washed with water (3×200 mL),dried over magnesium sulfate, and concentrated to a brown semi-solid. Silica gel flash chromatography using 5% methanol/chloroform as the eluent yielded 8-Chloro-3-{3-[5-(4-fluoro-phenyl)-2,5-diaza-bicyclo[2.2.2]oct-2-yl]-propyl}-1H-quinazoline-2,4-dione (0.18 g, 32.7%) as an light brown solid Maleate salt was formed by dissolving the solid in hot ethyl acetate (5 ml) and maleic acid (0.57 g, 1.2 eq) in ethyl acetate (4 ml) was added. Upon cooling the white solid was filtered to yield the maleate salt (0.12 g) which had the following properties: Mp. 186-188° C.; 1H NMR DMSO-d6 δ: 11.04 (brds, 1H), 9.40 (brd s, 1H), 7.91 (d, J=7.9 Hz, 1H), 7.79 (d, J=7.9 Hz, 1H), 7.20 (t, J=7.9 Hz, 1H), 6.68 (brds, 2H), 6.02 (s, 2H), 4.11 (brds, 1H), 4.02-3.92 (m, 2H), 3.80-3.52 (m, 3H), 3.44-3.17 (m, 4H), 2.18-1.65 9m, 6H). IR(KBr): Analysis calculated for C23H24ClFN4O2* C4H4O4: C, 56.40; H, 4.91; N, 9.74;

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. extractionextracted with ethyl acetate (3×100 mL)
  3. washThe pooled organic layers were washed with water (3×200 mL),dried over magnesium sulfate
  4. concentrationconcentrated to a brown semi-solid

Sources & evidence

ORD record
ord-a309de205d894148bce9d0d49b5d150e
Source dataset
uspto-grants-2003_04
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US06552015B2

Reaction notes

Loading…

On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes