Formic Acid → N-(4-(methoxymethyl)-5-(thiazolo[5,4-c]pyridin-2-yl)thiazol-2-yl)acetamide

HRID 2109701Notes

Reaction equation

HRID 2109701 reaction equation
C(N(CC)C([S:6][C:7]1[CH:8]=[N:9][CH:10]=[CH:11][C:12]=1[NH:13][C:14]([C:16]1[S:20][C:19]([NH:21][C:22](=[O:24])[CH3:23])=[N:18][C:17]=1[CH2:25][O:26][CH3:27])=O)=S)C.C(O)=O.Cl.CO>C(Cl)Cl>[CH3:27][O:26][CH2:25][C:17]1[N:18]=[C:19]([NH:21][C:22](=[O:24])[CH3:23])[S:20][C:16]=1[C:14]1[S:6][C:7]2[CH:8]=[N:9][CH:10]=[CH:11][C:12]=2[N:13]=1

Participants

6

Reactant 4

HCID 284Formic AcidHCID 313Hydrochloric AcidHCID 887MethanolHCID 576341864-(2-Acetamido-4-(methoxymethyl)thiazole-5-carboxamido)pyridin-3-yl diethylcarbamodithioate

Product 1

HCID 57633920N-(4-(methoxymethyl)-5-(thiazolo[5,4-c]pyridin-2-yl)thiazol-2-yl)acetamideYield 14.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Crude 4-(2-acetamido-4-(methoxymethyl)thiazole-5-carboxamido)pyridin-3-yl diethylcarbamodithioate (4.485 g, 9.89 mmol) and formic acid (0.379 mL, 9.89 mmol) were added to a 150 mL round-bottomed flask, and the solution was stirred at reflux for approximately 24 hours until LCMS indicated that the reaction was complete. The formic acid was removed, and the reaction was quenched by addition of 1 N NaOH. No precipitate formed, and the solution was made neutral with HCl and extracted with EtOAc (5×75 mL) to provide crude product. The organic solution was adsorbed onto a plug of silica gel and chromatographed through a Redi-Sep® pre-packed silica gel column (40 g), eluting with a gradient of 2% to 10% 2 M NH3.MeOH in DCM, to provide N-(4-(methoxymethyl)-5-(thiazolo[5,4-c]pyridin-2-yl)thiazol-2-yl)acetamide (0.446 g, 1.39 mmol, 14.1% yield). LCMS (M+H) 321.1 calc. for C13H13N4O2S2 321.39, 1H NMR (400 MHz, CD3OD): δ ppm 9.42 (s, 1H), 8.61 (d, J=6.5 Hz, 1H), 8.18 (d, J=6.5 Hz, 1H), 4.82 (s, 2H), 3.51 (s, 3H), 2.27 (s, 3H).

Workup

  1. temperatureat reflux for approximately 24 hours until LCMS
  2. customThe formic acid was removed
  3. customthe reaction was quenched by addition of 1 N NaOH
  4. customNo precipitate formed
  5. extractionextracted with EtOAc (5×75 mL)
  6. customto provide crude product
  7. customchromatographed through a Redi-Sep® pre-packed silica gel column (40 g)
  8. washeluting with a gradient of 2% to 10% 2 M NH3

Sources & evidence

ORD record
ord-9dc397ec797045a68fd174901612af9c
Source dataset
uspto-grants-2009_04
Patent number
US07514566B2

Reaction notes

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