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

HRID 1927474Notes

Reaction equation

HRID 1927474 reaction equation
[NH:1]1[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:6][O:7][C:8]([C:10]1[CH:11]=[C:12]([CH3:32])[C:13]2[O:19][C:18]3[C:20]([Cl:28])=[CH:21][C:22]([NH:24][CH2:25][CH2:26]Cl)=[CH:23][C:17]=3[CH2:16][S:15](=[O:30])(=[O:29])[C:14]=2[CH:31]=1)=[O:9]>CN(C=O)C>[CH3:6][O:7][C:8]([C:10]1[CH:11]=[C:12]([CH3:32])[C:13]2[O:19][C:18]3[C:20]([Cl:28])=[CH:21][C:22]([NH:24][CH2:25][CH2:26][N:1]4[CH2:5][CH2:4][CH2:3][CH2:2]4)=[CH:23][C:17]=3[CH2:16][S:15](=[O:29])(=[O:30])[C:14]=2[CH:31]=1)=[O:9]

Participants

4

Reactant 2

HCID 31268PyrrolidineHCID 1317284464-Chloro-2-(2-chloro-ethylamino)-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]-cycloheptene-8-carboxylic acid methyl ester

Product 1

HCID 1317284574-Chloro-6-methyl-10,10-dioxo-2-(2-pyrrolidin-1-yl-ethylamino)-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]cycloheptene-8-carboxylic acid methyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

Pyrrolidine (0.14 mL, 1.74 mmol) was added to a solution of Example 56k (0.5 g, 1.16 mmol) in dry DMF (5 mL) in an atmosphere of nitrogen. It was stirred at 100° C. for 5 h. The reaction mixture was concentrated and treated with chilled water to obtain a solid which was filtered, washed with water, dried and purified using flash chromatography (silica gel, 2% methanol/chloroform) to obtain the title compound. Yield: 0.375 g, (69.44%); 1H NMR (DMSO-d6): δ 1.75 (m, 4H, 2CH2), 2.70 (s, 3H, CH3), 2.85 (m, 2H, CH2), 3.20 (m, 2H, CH2), 3.90 (s, 3H, OCH3), 5.20 (s, 2H, CH2), 6.25 (t, 1H, NH), 6.7 (s, 2H, 2Ar), 8.20 (s, 1H, Ar), 8.25 (s, 1H, Ar); MS: m/e (ES−) 463 (M+).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. additiontreated with chilled water
  3. customto obtain a solid which
  4. filtrationwas filtered
  5. washwashed with water
  6. customdried
  7. custompurified

Sources & evidence

ORD record
ord-390a1d994a8a4f9cb4a578bad22dad66
Source dataset
uspto-grants-2012_05
Patent number
US08183234B2

Reaction notes

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