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

HRID 661028ノート

反応式

HRID 661028 の反応式
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

参加物

6

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-91d0af3a99da413a8b2db8fcf53029a1
出典データセット
uspto-grants-2011_12
特許番号
US08084479B2

反応ノート

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