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

HRID 1927503Notes

Reaction equation

HRID 1927503 reaction equation
[NH2:1][CH2:2][CH2:3][N:4]1[CH2:8][CH2:7][CH2:6][CH2:5]1.Cl[CH2:10][CH2:11][N:12]([CH2:35][CH2:36]Cl)[C:13]1[CH:33]=[C:32]([Cl:34])[C:16]2[O:17][C:18]3[C:27]([CH3:28])=[CH:26][C:25]([C:29]([OH:31])=[O:30])=[CH:24][C:19]=3[S:20](=[O:23])(=[O:22])[CH2:21][C:15]=2[CH:14]=1.[CH3:38]O>>[CH3:38][O:31][C:29]([C:25]1[CH:26]=[C:27]([CH3:28])[C:18]2[O:17][C:16]3[C:32]([Cl:34])=[CH:33][C:13]([N:12]4[CH2:11][CH2:10][N:1]([CH2:2][CH2:3][N:4]5[CH2:8][CH2:7][CH2:6][CH2:5]5)[CH2:36][CH2:35]4)=[CH:14][C:15]=3[CH2:21][S:20](=[O:23])(=[O:22])[C:19]=2[CH:24]=1)=[O:30]

Participants

4

Reactant 3

HCID 887MethanolHCID 13441-PyrrolidineethanamineHCID 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 1317284854-Chloro-6-methyl-10,10-dioxo-2-[4-(2-pyrrolidin-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

1-(2-Aminoethyl)pyrrolidine (1.60 mL, 12.6 mmol) was added to a solution of Example 102j (0.75 g, 1.50 mmol) in methanol (5 mL), in an atmosphere of nitrogen and sealed in a pressure reactor vessel at 110° C. for 5 h. The reaction mixture was brought to room temperature, concentrated, 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, brine, dried, concentrated and purified using flash chromatography (silica gel, 5% methanol/chloroform) to obtain the title compound. Yield: 0.320 g, (30.5%); 1H NMR (DMSO-d6): δ 1.90-1.95 (m, 4H, 2CH2), 2.62 (s, 6H, 2CH3), 2.70 (s, 3H, CH3), 3.10-3.15 (m, 8H, 4CH2), 3.20-3.25 (m, 4H, 2CH2), 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), 8.15 (s, 1H, Ar); MS: m/e (CI+) 534 (M+).

Workup

  1. customsealed in a pressure reactor vessel at 110° C. for 5 h
  2. customwas brought to room temperature
  3. concentrationconcentrated
  4. additiontreated with methanolic HCl solution
  5. concentrationThe reaction mixture was concentrated
  6. additiontreated with aqueous sodium bicarbonate solution to neutral pH
  7. extractionextracted with n-butanol
  8. washThe organic layer was washed with water, brine
  9. customdried
  10. concentrationconcentrated
  11. custompurified

Sources & evidence

ORD record
ord-abbf314e794842d3914438c10687df5d
Source dataset
uspto-grants-2012_05
Patent number
US08183234B2

Reaction notes

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