(2-Thienylmethyl)amine → HCID 131728468, compound

HRID 1927485Notes

Reaction equation

HRID 1927485 reaction equation
[NH2:1][CH2:2][C:3]1[S:4][CH:5]=[CH:6][CH:7]=1.[CH3:8][O:9][C:10]([C:12]1[CH:13]=[C:14]([CH3:34])[C:15]2[O:21][C:20]3[C:22]([Cl:30])=[CH:23][C:24]([NH:26][CH2:27][CH2:28]Cl)=[CH:25][C:19]=3[CH2:18][S:17](=[O:32])(=[O:31])[C:16]=2[CH:33]=1)=[O:11]>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CO>[CH3:8][O:9][C:10]([C:12]1[CH:13]=[C:14]([CH3:34])[C:15]2[O:21][C:20]3[C:22]([Cl:30])=[CH:23][C:24]([NH:26][CH2:27][CH2:28][NH:1][CH2:2][C:3]4[S:4][CH:5]=[CH:6][CH:7]=4)=[CH:25][C:19]=3[CH2:18][S:17](=[O:31])(=[O:32])[C:16]=2[CH:33]=1)=[O:11]

Participants

5

Reactant 2

HCID 34005(2-Thienylmethyl)amineHCID 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 131728468HCID 131728468, compound

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 887MethanolSolvent

Conditions

Temperature
110 °C

Procedure

2-Aminomethyl thiophene (0.38 g, 3.363 mmol) and tetrabutylammonium iodide (0.02 g, 0.054 mmol) were added to a suspension of the carboxylic acid of Example 56k (0.4 g, 0.96 mmol) in methanol (5 mL) under nitrogen in a pressure reactor vessel and heated to 110° C. for 4 h. The reaction mixture was concentrated (oily residue), treated with methanolic HCl (15 mL) and refluxed for 3.5 h. It was concentrated, treated with an aqueous sodium bicarbonate solution to pH 8 and extracted with chloroform. The organic layer was washed with water, brine, dried, concentrated and purified using flash chromatography (silica gel, 0.5% methanol/chloroform) to obtain the title compound. Yield: 0.21 g, (43.5%). 1H NMR (CDCl3): δ 2.68 (s, 3H, CH3), 2.98 (t, 2H, CH2), 3.18 (t, 2H, CH2), 3.9 (s, 3H, CH3), 4.6 (s, 2H, CH2), 4.67 (s, 1H, NH), 5.21 (s, 2H, CH2), 6.50 (s, 1H, Ar), 6.55 (s, 1H, Ar), 6.95 (s, 2H, Ar), 7.2 (m, 1H, Ar), 8.05 (s, 1H, Ar), 8.45 (s, 1H, Ar); MS: m/e (ES+) 505 (M+1).

Workup

  1. concentrationThe reaction mixture was concentrated (oily residue)
  2. additiontreated with methanolic HCl (15 mL)
  3. temperaturerefluxed for 3.5 h
  4. concentrationIt was concentrated
  5. additiontreated with an aqueous sodium bicarbonate solution to pH 8
  6. extractionextracted with chloroform
  7. washThe organic layer was washed with water, brine
  8. customdried
  9. concentrationconcentrated
  10. custompurified

Sources & evidence

ORD record
ord-49a3072c58724c4eb3b8946eab4c9733
Source dataset
uspto-grants-2012_05
Patent number
US08183234B2

Reaction notes

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