Acetaldehyde ammonia → 4-Chloro-2-[4-(2-hydroxy-ethyl)-piperazine-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 1173364Notes

Reaction equation

HRID 1173364 reaction equation
ClCC[N:4]([CH2:27][CH2:28]Cl)C1C=C(Cl)C2OC3C(C)=CC(C(O)=O)=CC=3S(=O)(=O)CC=2C=1.[CH3:30][O:31][C:32]([C:34]1[CH:35]=[C:36]([CH3:59])[C:37]2[O:43][C:42]3[C:44]([Cl:55])=[CH:45][C:46]([N:48]([CH2:52][CH2:53]Cl)[CH2:49][CH2:50]Cl)=[CH:47][C:41]=3[CH2:40][S:39](=[O:57])(=[O:56])[C:38]=2[CH:58]=1)=[O:33].NC([OH:63])C>CO>[CH3:30][O:31][C:32]([C:34]1[CH:35]=[C:36]([CH3:59])[C:37]2[O:43][C:42]3[C:44]([Cl:55])=[CH:45][C:46]([N:48]4[CH2:49][CH2:50][N:4]([CH2:27][CH2:28][OH:63])[CH2:53][CH2:52]4)=[CH:47][C:41]=3[CH2:40][S:39](=[O:57])(=[O:56])[C:38]=2[CH:58]=1)=[O:33]

Participants

5

Reactant 3

HCID 522583Acetaldehyde ammoniaHCID 115260722-[Bis-(2-chloro-ethyl)-amino]-4-chloro-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carboxylic acid methyl esterHCID 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 116915114-Chloro-2-[4-(2-hydroxy-ethyl)-piperazine-1-yl]-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carboxylic acid methyl ester

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 2-[bis-(2-chloroethyl)amino]-4-chloro-6-methyl10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]-cycloheptene-8-carboxylic acid [prepared by hydrolysis of compound of Example 12, 0.5 g, 1.044 mmol], in methanol (8 mL), aminoethanol (0.25 mL, 4.17 mmol) was added and heated to 120° C. in a sealed reactor for 4 h. The reaction mixture was cooled and the solvent was removed under reduced pressure. To the residue, methanolic HCl (20 mL) was added and refluxed for 3 h. Solvent was removed and the reaction mixture was basified to pH 8 using sodium carbonate solution and extracted using ethyl acetate (3×25 mL). The organic layer was washed with water and brine solution, concentrated and the crude product was purified by column chromatography (silica gel, 1% methanol in chloroform) to obtain the title compound. Yield: 0.317 g, (67.13%); 1H NMR (DMSO-d6, 300 MHz): δ 2.4 (t, 2H, CH2), 2.48 (s, 4H, 2CH2), 2.63 (s, 3H, CH3), 3.17 (s, 4H, 2CH2), 3.41 (t, 2H, CH2), 3.86 (s, 3H, OCH3), 4.44 (t, 1H, OH), 5.15 (s, 2H, CH2), 7.04 (s, 1H, Ar), 7.12 (s, 1H, Ar), 8.08 (s, 1H, Ar), 8.15 (s, 1H, Ar); MS: m/e (ES+) 481 (M+1); analysis: C22H25ClN2O6S requires C, 54.94; H, 5.24; N, 5.82; Cl, 7.37; S, 6.67. found: C, 54.78; H, 5.34; N, 5.7; Cl, 7.87; S, 6.88%.

Workup

  1. temperatureThe reaction mixture was cooled
  2. customthe solvent was removed under reduced pressure
  3. additionTo the residue, methanolic HCl (20 mL) was added
  4. temperaturerefluxed for 3 h
  5. customSolvent was removed
  6. extractionextracted
  7. washThe organic layer was washed with water and brine solution
  8. concentrationconcentrated
  9. customthe crude product was purified by column chromatography (silica gel, 1% methanol in chloroform)

Sources & evidence

ORD record
ord-4f8870c8d53942c8bd4b70af8b35e5c7
Source dataset
uspto-grants-2010_11
Patent number
US07834052B2

Reaction notes

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