Ammonia → 4-Chloro-6-methyl-10,10-dioxo-2-piperazin-1-yl-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cyclo heptene-8-carboxylic acid methyl ester

HRID 1927493Notes

Reaction equation

HRID 1927493 reaction equation
[NH3:1].Cl[CH2:3][CH2:4][N:5]([CH2:28][CH2:29]Cl)[C:6]1[CH:26]=[C:25]([Cl:27])[C:9]2[O:10][C:11]3[C:20]([CH3:21])=[CH:19][C:18]([C:22]([OH:24])=[O:23])=[CH:17][C:12]=3[S:13](=[O:16])(=[O:15])[CH2:14][C:8]=2[CH:7]=1.[CH3:31]O>>[CH3:31][O:24][C:22]([C:18]1[CH:19]=[C:20]([CH3:21])[C:11]2[O:10][C:9]3[C:25]([Cl:27])=[CH:26][C:6]([N:5]4[CH2:4][CH2:3][NH:1][CH2:29][CH2:28]4)=[CH:7][C:8]=3[CH2:14][S:13](=[O:15])(=[O:16])[C:12]=2[CH:17]=1)=[O:23]

Participants

4

Reactant 3

HCID 222AmmoniaHCID 887MethanolHCID 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 115410724-Chloro-6-methyl-10,10-dioxo-2-piperazin-1-yl-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cyclo heptene-8-carboxylic acid methyl ester

Conditions

Temperature
110 °C

Procedure

Aqueous ammonia solution (30%, 4 mL) was added to a solution of Example 102j (0.5 g, 1.04 mmol) in methanol (1 mL), in an atmosphere of nitrogen, sealed in a pressure reactor vessel and heated at 110° C. for 6 h. The reaction mixture was brought to room temperature, concentrated, treated with chilled water and dilute HCl to neutral pH. The solid that precipitated was filtered, washed with water and dried. It was treated with methanolic HCl solution and stirred at 70° C. for 2.5 h. The reaction mixture was cooled and the solid that separated was filtered, washed with methanol, dried and purified using flash chromatography (silica gel, MeOH/CHCl3) to obtain the title compound as an off white solid. Yield: 0.220 g (48.24%); 1H NMR (DMSO-d6): δ 2.30 (m, 4H, 2CH2), 2.70 (s, 3H, CH3), 3.10 (m, 4H, 2CH2), 3.95 (s, 3H, OCH3), 5.10 (s, 2H, CH2), 7.10 (s, 1H, Ar), 7.20 (s, 1H, Ar), 8.05 (s, 1H, Ar) 8.20 (s, 1H, Ar): MS: m/e (ES+) 422 (M+1).

Workup

  1. customsealed in a pressure reactor vessel
  2. customwas brought to room temperature
  3. concentrationconcentrated
  4. additiontreated with chilled water and dilute HCl to neutral pH
  5. customThe solid that precipitated
  6. filtrationwas filtered
  7. washwashed with water
  8. customdried
  9. additionIt was treated with methanolic HCl solution
  10. temperatureThe reaction mixture was cooled
  11. customthe solid that separated
  12. filtrationwas filtered
  13. washwashed with methanol
  14. customdried
  15. custompurified

Sources & evidence

ORD record
ord-570bd6a3c83e49249c769e5c31afba64
Source dataset
uspto-grants-2012_05
Patent number
US08183234B2

Reaction notes

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