4-Chloro-3-methoxyaniline → 5-(3,4-Dimethoxy-phenyl)-thiomorpholine-3-carboxylic acid (4-chloro-3-methoxy-phenyl)-amide

HRID 1294611Notes

Reaction equation

HRID 1294611 reaction equation
C[Al](C)C.CO[C:7]([CH:9]1[CH2:14][S:13][CH2:12][CH:11]([C:15]2[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[C:17]([O:23][CH3:24])[CH:16]=2)[NH:10]1)=[O:8].[Cl:25][C:26]1[CH:32]=[CH:31][C:29]([NH2:30])=[CH:28][C:27]=1[O:33][CH3:34]>>[Cl:25][C:26]1[CH:32]=[CH:31][C:29]([NH:30][C:7]([CH:9]2[CH2:14][S:13][CH2:12][CH:11]([C:15]3[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[C:17]([O:23][CH3:24])[CH:16]=3)[NH:10]2)=[O:8])=[CH:28][C:27]=1[O:33][CH3:34]

Participants

4

Reactant 3

HCID 131036924-Chloro-3-methoxyanilineHCID 16682925TrimethylaluminumHCID 651713775-(3,4-Dimethoxy-phenyl)-thiomorpholine-3-carboxylic acid methyl ester

Product 1

HCID 865972335-(3,4-Dimethoxy-phenyl)-thiomorpholine-3-carboxylic acid (4-chloro-3-methoxy-phenyl)-amide

Conditions

Temperature
50 °C

Procedure

A 2.0M solution of trimethylaluminum (0.39 ml, 0.78 mmol, 3.5 equivalents) was added to a solution of 5-(3,4-dimethoxy-phenyl)-thiomorpholine-3-carboxylic acid methyl ester (67 mg, 0.22 mmol, 1.0 equivalents) and 4-chloro-3-methoxyaniline (106 mg, 0.68 mmol, 3.0 equivalents). The solution was stirred at 50° C. for 18 hours. The reaction was quenched with 1N NaOH and extracted with dichloromethane. The dichloromethane extracts were dried with MgSO4, filtered and concentrated. The residue was purified on a 1000 micron preparative TLC. 5-(3,4-Dimethoxy-phenyl)-thiomorpholine-3-carboxylic acid (4-chloro-3-methoxy-phenyl)-amide was obtained as a peach solid (71 mg, 76% yield). Analysis H1 NMR (400 MHz, CDCl3): 8.61 (1H, s), 7.58 (1H, m), 7.26 (1H, m), 6.90 (2H, m), 6.78 (1H, d), 4.04 (1H, m), 3.91 (10H, m), 2.98 (1H, m), 2.78 (2H, m), 2.59 (1H, m). MS (LC-MS): Calculated for C20H23ClN2O4S 423.11. Found 423.22.

Workup

  1. customThe reaction was quenched with 1N NaOH
  2. extractionextracted with dichloromethane
  3. dry with materialThe dichloromethane extracts were dried with MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified on a 1000 micron preparative TLC

Sources & evidence

ORD record
ord-224c188be91b4810a59c7fa9360e9e65
Source dataset
uspto-grants-2007_07
Patent number
US07241765B2

Reaction notes

Loading…