Trifluoroacetic acid → 4-{4-[3-(6-Piperidin-1-ylmethyl-pyridin-2-yl)-ureido]-thiazol-2-yl)-benzenesulfonamide

HRID 460259Notes

Reaction equation

HRID 460259 reaction equation
C([C:3]1[S:7][C:6]([C:8]2[CH:13]=[CH:12][C:11]([S:14](=[O:17])(=[O:16])[NH2:15])=[CH:10][CH:9]=2)=[N:5][C:4]=1C(O)=O)C.P([N:37]=[N+]=[N-])(OC1C=CC=CC=1)(OC1C=CC=CC=1)=O.[N:40]1([CH2:46][C:47]2[N:52]=[C:51]([NH2:53])[CH:50]=[CH:49][CH:48]=2)[CH2:45][CH2:44][CH2:43][CH2:42][CH2:41]1.[C:54]([OH:60])(C(F)(F)F)=O>>[N:40]1([CH2:46][C:47]2[N:52]=[C:51]([NH:53][C:54](=[O:60])[NH:37][C:4]3[N:5]=[C:6]([C:8]4[CH:9]=[CH:10][C:11]([S:14]([NH2:15])(=[O:16])=[O:17])=[CH:12][CH:13]=4)[S:7][CH:3]=3)[CH:50]=[CH:49][CH:48]=2)[CH2:41][CH2:42][CH2:43][CH2:44][CH2:45]1

Participants

5

Reactant 4

HCID 6422Trifluoroacetic acidHCID 123414Diphenylphosphoryl azideHCID 187716712-Amino-6-(piperidin-1-ylmethyl)pyridineHCID 18771914Ethyl 2-(4-sulfamoyl-phenyl)-1,3-thiazole-4-carboxylic acid

Product 1

HCID 187717374-{4-[3-(6-Piperidin-1-ylmethyl-pyridin-2-yl)-ureido]-thiazol-2-yl)-benzenesulfonamide

Procedure

To a stirred solution of ethyl 2-(4-sulfamoyl-phenyl)-1,3-thiazole-4-carboxylic acid (90 mg, 0.32 mmol) in dry TFA (3 mL) and 4A molecular sieves at RT and under N2 was added TEA (0.1 mL). After 5 min, (PhO)2PON3 (0.11 mL) and 6-(piperidylmethyl)-2-pyridylamine (0.10 g, 0.51 mmol) were added and the reaction mixture was heated to reflux for 4 h and then cooled to RT. The mixture was washed with 10% HCl (aq) and extracted with EtOAc (3×10 mL). The aqueous layer was brought to a pH 8.0 and extracted with CH2Cl2 (3×20 mL). The extracts were combined, dried over MgSO4, concentrated by rotary evaporation and purified on silica gel (2:1 hexanes/EtOAc and 1:1 MeOH/CH2Cl2) to afford the title compound as a pale yellow solid. EI-MS m/z 473 (M+H). Calc'd for C21H24N6O3S2: 472.14.

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureto reflux for 4 h
  3. washThe mixture was washed with 10% HCl (aq)
  4. extractionextracted with EtOAc (3×10 mL)
  5. extractionextracted with CH2Cl2 (3×20 mL)
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated by rotary evaporation
  8. custompurified on silica gel (2:1 hexanes/EtOAc and 1:1 MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-caa377de708b493181abc8053c8be78d
Source dataset
uspto-grants-2007_03
Patent number
US07196104B2

Reaction notes

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