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

HRID 1172545Notes

Reaction equation

HRID 1172545 reaction equation
[C:1]1([CH3:11])[CH:6]=CC(S(O)(=O)=O)=[CH:3][CH:2]=1.[NH2:12][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.[C:35]([BH3-])#[N:36].[Na+].[C:39](=O)(O)[O-].[Na+]>C1C=CC=CC=1>[CH3:39][O:30][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]([NH:12][CH2:11][C:1]4[CH:6]=[N:36][CH:35]=[CH:3][CH:2]=4)=[CH:14][C:15]=3[CH2:21][S:20](=[O:22])(=[O:23])[C:19]=2[CH:24]=1)=[O:31]

Participants

6

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 516892Sodium BicarbonateHCID 5003444Sodium cyanoborohydrideHCID 116317172-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 1317285124-Chloro-6-methyl-10,10-dioxo-2-[(pyridin-3-ylmethyl)-amino]-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carboxylic acid methyl ester

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Conditions

Temperature
25 °C

Procedure

Pyridine-3-carboxyaldehyde (0.1 mL, 1.08 mmol) and p-toluene sulfonic acid (in catalytic amount) were added to a suspension of Example 35j (0.4 g, 1.08 mmol) in benzene (40 mL). The reaction mixture was refluxed using Dean-Stark apparatus for 4 h. It was concentrated, treated with methanol, refluxed for 4 h, and stirred at 25° C. overnight. Sodium cyanoborohydride (0.076 g, 1.2 mmol) was added and the reaction mixture was stirred for 3 h. It was treated with aqueous sodium bicarbonate solution and extracted with ethyl acetate. The organic layer was washed with water, brine, dried, concentrated and purified using flash chromatography (silica gel, methanol/chloroform) to obtain the title compound. Yield: 0.127 g, (25%); 1H NMR (DMSO-d6): δ 2.62 (s, 3H, CH3), 3.9 (s, 3H, CH3), 4.33 (d, 2H, CH2), 5.18 (s, 2H, CH2), 6.69 (d, 1H, Ar), 6.8 (d, 1H, Ar), 6.9 (t, 1H, NH), 7.38 (q, 1H, Ar), 7.75 (d, 1H, Ar), 8.1 (s, 1H, Ar), 8.17 (s, 1H, Ar), 8.48 (d, 1H, Ar), 8.6 (s, 1H, Ar).

Workup

  1. temperatureThe reaction mixture was refluxed
  2. customfor 4 h
  3. concentrationIt was concentrated
  4. additiontreated with methanol
  5. temperaturerefluxed for 4 h
  6. stirringthe reaction mixture was stirred for 3 h
  7. extractionextracted with ethyl acetate
  8. washThe organic layer was washed with water, brine
  9. customdried
  10. concentrationconcentrated
  11. custompurified

Sources & evidence

ORD record
ord-a963bddaf2e44882bce490cf31c7b675
Source dataset
uspto-grants-2010_11
Patent number
US07834001B2

Reaction notes

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