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

HRID 1172517Notes

Reaction equation

HRID 1172517 reaction equation
[NH2:1][CH2:2][CH2:3][N:4]1[CH2:9][CH2:8][NH:7][CH2:6][CH2:5]1.Cl[CH2:11][CH2:12][N:13]([CH2:36][CH2:37]Cl)[C:14]1[CH:34]=[C:33]([Cl:35])[C:17]2[O:18][C:19]3[C:28]([CH3:29])=[CH:27][C:26]([C:30]([OH:32])=[O:31])=[CH:25][C:20]=3[S:21](=[O:24])(=[O:23])[CH2:22][C:16]=2[CH:15]=1.[CH3:39]O>>[CH3:39][O:32][C:30]([C:26]1[CH:27]=[C:28]([CH3:29])[C:19]2[O:18][C:17]3[C:33]([Cl:35])=[CH:34][C:14]([N:13]4[CH2:12][CH2:11][N:1]([CH2:2][CH2:3][N:4]5[CH2:9][CH2:8][NH:7][CH2:6][CH2:5]5)[CH2:37][CH2:36]4)=[CH:15][C:16]=3[CH2:22][S:21](=[O:23])(=[O:24])[C:20]=2[CH:25]=1)=[O:31]

Participants

4

Reactant 3

HCID 887MethanolHCID 8795AminoethylpiperazineHCID 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 1317284874-Chloro-6-methyl-10,10-dioxo-2-[4-(2-piperazin-1-yl-ethyl)-piperazin-1-yl]-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carboxylic acid methyl ester

Conditions

Temperature
70 °C

Procedure

N-Aminoethyl piperazine (0.6 mL, 5.2 mmol) was added to a solution of Example 102j (0.5 g, 1.04 mmol) in methanol (5 mL), followed by the addition of n-tetrabutylammonium iodide (0.075 g, 0.20 mmol) in an atmosphere of nitrogen, in a pressure reactor vessel at 120° C. for 5 h. The reaction mixture was brought to room temperature, concentrated and treated with water. The solid that separated was washed with water, dried, treated with methanolic HCl solution, and refluxed at 70° C. for 2 h. The reaction mixture was concentrated, treated with aqueous sodium bicarbonate solution to neutral pH and extracted with n-butanol. The organic layer was washed with water, dried, concentrated and purified using flash chromatography (silica gel, 20% methanol/chloroform) to obtain the title compound. Yield: 0.075 g, (13%); 1H NMR (DMSO-d6): δ 2.50-2.60 (m, 4H, 2CH2), 2.70 (s, 3H, CH3), 3.00-3.40 (m, 14H, 7CH2), 3.70 (s, 1H, OH), 3.90 (s, 3H, OCH3), 5.20 (s, 2H, CH2), 7.10 (s, 1H, Ar), 7.20 (s, 1H, Ar), 8.10 (s, 1H, Ar), 8.20 (s, 1H, Ar); MS: m/e (EI+) 459 (M+1).

Workup

  1. customwas brought to room temperature
  2. concentrationconcentrated
  3. additiontreated with water
  4. customThe solid that separated
  5. washwas washed with water
  6. customdried
  7. additiontreated with methanolic HCl solution
  8. concentrationThe reaction mixture was concentrated
  9. additiontreated with aqueous sodium bicarbonate solution to neutral pH
  10. extractionextracted with n-butanol
  11. washThe organic layer was washed with water
  12. customdried
  13. concentrationconcentrated
  14. custompurified

Sources & evidence

ORD record
ord-645334b0977142ecb8415fa378275f97
Source dataset
uspto-grants-2010_11
Patent number
US07834001B2

Reaction notes

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