Methanol → 4-Chloro-6-methyl-10,10-dioxo-2-(4-pyridin-3-ylmethyl-piperazin-1-yl)-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carboxylic acid methyl ester

HRID 1927509Notes

Reaction equation

HRID 1927509 reaction equation
[NH2:1][CH2:2][C:3]1[CH:4]=[N:5][CH:6]=[CH:7][CH:8]=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][C:3]5[CH:4]=[N:5][CH:6]=[CH:7][CH:8]=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 310183-PyridinemethanamineHCID 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 1317284914-Chloro-6-methyl-10,10-dioxo-2-(4-pyridin-3-ylmethyl-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

3-Aminomethyl-pyridine (0.66 mL, 6.25 mmol) was added to a solution of Example 102j (0.6 g, 1.25 mmol) in methanol (10 mL), followed by addition of n-tetrabutylammonium iodide (0.010 g, 0.027 mmol) in an atmosphere of nitrogen and sealed in a pressure reactor vessel at 110° C. for 6 h. The reaction mixture was brought to room temperature, concentrated, treated with methanolic HCl solution, and refluxed at 70° C. for 6 h. It 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: 0.160 g, (25%); 1H NMR (DMSO-d6): δ 2.70 (s, 3H, CH3), 3.20-3.60 (m, 8H, 4CH2), 3.65 (s, 2H, CH2), 3.90 (s, 3H, OCH3), 5.10 (s, 2H, CH2), 7.05 (s, 1H, Ar), 7.20 (s, 1H, Ar), 7.40 (t, 1H, Ar), 7.75 (d, 1H, Ar), 8.10 (s, 1H, Ar), 8.20 (s, 1H, Ar), 8.50 (d, 1H, Ar), 8.55 (s, 1H, Ar); MS: m/e (CI+) 528 (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. concentrationIt 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-72628c3b4a0d4607beab828c3a82fd94
Source dataset
uspto-grants-2012_05
Patent number
US08183234B2

Reaction notes

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