Ethanol → HCID 178522939, compound

HRID 1978963Notes

Reaction equation

HRID 1978963 reaction equation
C=O.[NH:3]1[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1.[CH2:9](O)C.[Cl:12][C:13]1[CH:32]=[CH:31][C:16]([CH2:17][NH:18][C:19]([C:21]2[C:22]([OH:30])=[C:23]3[CH:29]=[CH:28][S:27][C:24]3=[N:25][CH:26]=2)=[O:20])=[CH:15][CH:14]=1>C(O)(=O)C>[Cl:12][C:13]1[CH:14]=[CH:15][C:16]([CH2:17][NH:18][C:19]([C:21]2[C:22]([OH:30])=[C:23]3[CH:29]=[C:28]([CH2:9][N:3]4[CH2:8][CH2:7][O:6][CH2:5][CH2:4]4)[S:27][C:24]3=[N:25][CH:26]=2)=[O:20])=[CH:31][CH:32]=1

Participants

6

Reactant 4

HCID 702EthanolHCID 712Formaldehyde2×HCID 8083Morpholine2×HCID 178522935HCID 178522935, compound

Product 1

HCID 178522939HCID 178522939, compoundYield 55%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

Formaldehyde (2.6 mL) is added to morpholine (2.7 mL) at 0° C. Ethanol (10 mL) is then added followed by addition of N-(4-chlorobenzyl)-4-hydroxythieno[2,3-b]pyridine-5-carboxamide (1.00 g) from Example No. 1. Acetic acid (2 mL) is added, and the reaction mixture is allowed to warm to rt and then refluxed for 18 h. Additional morpholine (2.7 mL) and formaldehyde (2.6 mL) are added and the reaction is refluxed for an additional 24 h. The reaction mixture is allowed to cool to room temperature and is then concentrated in vacuo. The residue is treated with 25% NaOH (20 mL). The aqueous layer is extracted with ethyl acetate (50 mL) then CHCl3 (60 mL). Methanol (30 mL) is added to the aqueous layer and it is extracted with CHCl3 (2×60 mL). This procedure is repeated 3 times. The combined organic layers are dried with MgSO4, filtered, and concentrated in vacuo. The resulting brown solid is purified by column chromatography (CH2Cl2/methanol, 98/2; 96/4) to yield a tan solid which is recrystallized from ethyl acetate/Et2O to yield 0.718 g (55%) of the title compound as an off-white solid.

Workup

  1. temperaturerefluxed for 18 h
  2. temperaturethe reaction is refluxed for an additional 24 h
  3. temperatureto cool to room temperature
  4. concentrationis then concentrated in vacuo
  5. additionThe residue is treated with 25% NaOH (20 mL)
  6. extractionThe aqueous layer is extracted with ethyl acetate (50 mL)
  7. additionMethanol (30 mL) is added to the aqueous layer and it
  8. extractionis extracted with CHCl3 (2×60 mL)
  9. dry with materialThe combined organic layers are dried with MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customThe resulting brown solid is purified by column chromatography (CH2Cl2/methanol, 98/2; 96/4)
  13. customto yield a tan solid which
  14. customis recrystallized from ethyl acetate/Et2O

Sources & evidence

ORD record
ord-640d58eb2e1346caaf0381823fc3daef
Source dataset
uspto-grants-2001_05
Patent number
US06239142B1

Reaction notes

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