Ethyl Acetate → 1-[2-(3-Methoxyphenyl)thiazol-4-yl]-3-(6-piperidin-1-ylmethyl-pyridin-2-yl)urea

HRID 479703Notes

Reaction equation

HRID 479703 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:9]2[S:10][CH:11]=[C:12](C(O)=O)[N:13]=2)[CH:6]=[CH:7][CH:8]=1.P([N:33]=[N+]=[N-])(OC1C=CC=CC=1)(OC1C=CC=CC=1)=O.[N:36]1([CH2:42][C:43]2[N:48]=[C:47]([NH2:49])[CH:46]=[CH:45][CH:44]=2)[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]1.CCO[C:53](C)=[O:54]>C1(C)C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:9]2[S:10][CH:11]=[C:12]([NH:33][C:53]([NH:49][C:47]3[CH:46]=[CH:45][CH:44]=[C:43]([CH2:42][N:36]4[CH2:37][CH2:38][CH2:39][CH2:40][CH2:41]4)[N:48]=3)=[O:54])[N:13]=2)[CH:6]=[CH:7][CH:8]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 123414Diphenylphosphoryl azideHCID 156230652-(3-Methoxyphenyl)-1,3-thiazole-4-carboxylic acidHCID 187716712-Amino-6-(piperidin-1-ylmethyl)pyridine

Product 1

HCID 187718021-[2-(3-Methoxyphenyl)thiazol-4-yl]-3-(6-piperidin-1-ylmethyl-pyridin-2-yl)urea

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
85 °C

Procedure

To a stirred solution of 2-(3-methoxyphenyl)-1,3-thiazole-4-carboxylic acid (0.17 g, 0.72 mmol) in toluene (10 mL) at RT and under N2 was added TEA (0.2 mL). After 5 min, (PhO)2PON3 (0.2 5 mL) was added and the reaction mixture was heated at 85° C. for 20 min followed by the addition of 6-(piperidylmethyl)-2-pyridylamine (0.21 g, 1.1 mmol). The resulting mixture was heated at reflux for 4 h using a Dean-Stark trap. The mixture was cooled to RT, concentrated by rotary evaporation and purified on silica gel (5:95 MeOH/CH2Cl2). The yellow solid obtained was dissolved in EtOAc (15 mL) and washed with a saturated solution of NH4Cl (aq). The organic phase was separated, dried over MgSO4, filtered and concentrated by rotary evaporation. The product was recrystallized from hexanes to afford the title compound as a white solid. EI-MS m/z 424 (M+H). Calc'd for C22H25N5O2S: 423.17.

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureat reflux for 4 h
  3. temperatureThe mixture was cooled to RT
  4. concentrationconcentrated by rotary evaporation
  5. custompurified on silica gel (5:95 MeOH/CH2Cl2)
  6. customThe yellow solid obtained
  7. washwashed with a saturated solution of NH4Cl (aq)
  8. customThe organic phase was separated
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated by rotary evaporation
  12. customThe product was recrystallized from hexanes

Sources & evidence

ORD record
ord-859da533c9284a74a137695618de185e
Source dataset
uspto-grants-2003_11
Patent number
US06645990B2

Reaction notes

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