Triethylamine → 2-Methoxymethyl-thiazolo[5,4-b]pyridin-6-yl-carboxylic acid-N-phenyl-N-(2-ethoxycarbonylethyl)-amide

HRID 50337Notes

Reaction equation

HRID 50337 reaction equation
[CH3:1][O:2][CH2:3][C:4]1[S:5][C:6]2[C:11]([N:12]=1)=[CH:10][C:9]([C:13]([OH:15])=O)=[CH:8][N:7]=2.S(Cl)(Cl)=[O:17].C(O[C:23](=[C:32]=[O:33])[CH2:24][NH:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)C.C(N([CH2:39][CH3:40])CC)C>C(Cl)Cl.O1CCCC1.C(OCC)(=O)C>[C:26]1([N:25]([CH2:24][CH2:23][C:32]([O:33][CH2:39][CH3:40])=[O:17])[C:13]([C:9]2[CH:10]=[C:11]3[N:12]=[C:4]([CH2:3][O:2][CH3:1])[S:5][C:6]3=[N:7][CH:8]=2)=[O:15])[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 184124392-Methoxymethyl-thiazolo[5,4-b]pyridin-6-yl-carboxylic acidHCID 86755521N-(2-ethoxy-carbonylethyl)aniline

Product 1

HCID 184125392-Methoxymethyl-thiazolo[5,4-b]pyridin-6-yl-carboxylic acid-N-phenyl-N-(2-ethoxycarbonylethyl)-amide

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A suspension of 1.03 g (4.62 mmol) of 2-methoxymethylthiazolo[5,4-b]pyridin-6-yl-carboxylic acid in 40 mL of methylene chloride was mixed with 1.6 g=1.0 mL (13.5 mmol) of thionyl chloride and refluxed for 90 minutes, during which time the solid gradually dissolved. After the liquid components had been distilled off, the crude product was taken up twice more in methylene chloride and concentrated again. The resulting crude acid chloride (1.2 g) was taken up in 40 mL of tetrahydrofuran, added dropwise to a mixture of 0.94 g (4.86 mmol) of N-(2-ethoxy-carbonylethyl)aniline and 2.1 mL (13.8 mmol) of triethylamine in 30 mL of tetrahydrofuran and stirred for 2 hours at room temperature. Then it was diluted with 200 mL of ethyl acetate, washed with 100 mL of 14% saline solution, and the organic phase was dried with sodium sulfate. After the solvent had been removed in vacuo, the crude product obtained was purified by flash chromatography (silica gel; methylene chloride/ethanol=100:1). Yield: 1.57 g (87% of theory)of yellow oil; Rf value: 0.55 (silica gel; methylene chloride/ethanol=19:1).

Workup

  1. temperaturerefluxed for 90 minutes, during which time the solid
  2. dissolutiongradually dissolved
  3. distillationAfter the liquid components had been distilled off
  4. concentrationconcentrated again
  5. washwashed with 100 mL of 14% saline solution
  6. dry with materialthe organic phase was dried with sodium sulfate
  7. customAfter the solvent had been removed in vacuo

Sources & evidence

ORD record
ord-192874638f704f7fbabfbedf320e425b
Source dataset
uspto-grants-2004_03
Patent number
US06710055B2

Reaction notes

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