Methanol → 4-Chloro-2-(4-cyclobutyl-piperazin-1-yl)-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carboxylic acid methyl ester

HRID 1172522Notes

Reaction equation

HRID 1172522 reaction equation
[CH:1]1([NH2:5])[CH2:4][CH2:3][CH2:2]1.Cl[CH2:7][CH2:8][N:9]([CH2:32][CH2:33]Cl)[C:10]1[CH:30]=[C:29]([Cl:31])[C:13]2[O:14][C:15]3[C:24]([CH3:25])=[CH:23][C:22]([C:26]([OH:28])=[O:27])=[CH:21][C:16]=3[S:17](=[O:20])(=[O:19])[CH2:18][C:12]=2[CH:11]=1.[CH3:35]O>>[CH3:35][O:28][C:26]([C:22]1[CH:23]=[C:24]([CH3:25])[C:15]2[O:14][C:13]3[C:29]([Cl:31])=[CH:30][C:10]([N:9]4[CH2:8][CH2:7][N:5]([CH:1]5[CH2:4][CH2:3][CH2:2]5)[CH2:33][CH2:32]4)=[CH:11][C:12]=3[CH2:18][S:17](=[O:20])(=[O:19])[C:16]=2[CH:21]=1)=[O:27]

Participants

4

Reactant 3

HCID 887MethanolHCID 75645CyclobutylamineHCID 1317284742-[Bis-(2-chloroethyl)amino]-4-chloro-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]-cycloheptene-8-carboxylic acid

Product 1

HCID 1317284924-Chloro-2-(4-cyclobutyl-piperazin-1-yl)-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carboxylic acid methyl ester

Conditions

Temperature
70 °C

Procedure

Cyclobutylamine (1 mL, excess) was added to a solution of Example 102j (0.6 g, 1.25 mmol) in methanol (10 mL), followed by the addition of n-tetrabutylammonium iodide (0.01 g, 0.027 mmol) in an atmosphere of nitrogen and sealed in a pressure reactor vessel at 110° C. for 6 h. It was brought to room temperature, concentrated, treated with methanolic HCl solution, and refluxed at 70° C. for 6 h. The reaction mixture was concentrated, treated with water, aqueous sodium bicarbonate solution to neutral pH and the solid that separated was washed with water dried, and purified using flash chromatography (silica gel, methanol/chloroform) to obtain the title compound as a white solid. Yield: 0.410 g, (25%); 1H NMR (DMSO-d6): δ 1.60-2.10 (m, 6H, 3CH2), 2.40-2.50 (m, 4H, 2CH2), 2.80 (m, 1H, CH), 3.20-3.30 (m, 4H, 2CH2), 3.90 (s, 3H, OCH3), 4.70 (s, 2H, CH2), 6.80 (s, 1H, Ar), 6.90 (s, 1H, Ar), 8.10 (s, 1H, Ar), 8.50 (s, 1H, Ar); MS: m/e (CI+) 491 (M+1).

Workup

  1. customsealed in a pressure reactor vessel at 110° C. for 6 h
  2. customwas brought to room temperature
  3. concentrationconcentrated
  4. additiontreated with methanolic HCl solution
  5. concentrationThe reaction mixture was concentrated
  6. additiontreated with water, aqueous sodium bicarbonate solution to neutral pH
  7. customthe solid that separated
  8. washwas washed with water
  9. customdried
  10. custompurified

Sources & evidence

ORD record
ord-643b17d2173a4e5e98844e647e9ab659
Source dataset
uspto-grants-2010_11
Patent number
US07834001B2

Reaction notes

Loading…