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

HRID 479705Notes

Reaction equation

HRID 479705 reaction equation
CO[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[S:10][CH:11]=[C:12]([NH:14][C:15]([NH:17][C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([CH2:24][N:25]3[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]3)[N:19]=2)=[O:16])[N:13]=1.[Cl-].[Be+2].[Cl-].CC[O:36]C(C)=O>C1(C)C=CC=CC=1>[OH:36][C:6]1[CH:5]=[C:4]([C:9]2[S:10][CH:11]=[C:12]([NH:14][C:15]([NH:17][C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([CH2:24][N:25]4[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]4)[N:19]=3)=[O:16])[N:13]=2)[CH:3]=[CH:8][CH:7]=1

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 24588Beryllium ChlorideHCID 187721331-[2-(2-Methoxyphenyl)thiazol-4-yl]-3-(6-piperidin-1-ylmethyl-pyridin-2-yl)urea

Product 1

HCID 187716961-[2-(3-Hydroxyphenyl)thiazol-4-yl]-3-(6-piperidin-1-ylmethyl-pyridin-2-yl)urea

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

A mixture of 1-[2-(3-methoxyphenyl)thiazol-4-yl]-3-(6-piperidin-1-ylmethyl-pyridin-2-yl)urea (Example 218) and beryllium chloride (5.0 eq) in dry toluene (0.2 M) and 4A molecular sieves was heated at reflux for 10 h. The starting material was not totally soluble in toluene. The mixture was brought to RT, diluted with EtOAc and washed with saturated NH4Cl. The organic phase was separated, dried over MgSO4, filtered, concentrated by rotary evaporation and purified by prep HPLC (Column Phenomenex type Prodigy 50 ODS3 100A size 250×21.20 mm 5u, Gradient 10% to 90% CH3CN:H2O containing 1% TFA over 20 min, Detector 254 nm, 4 nm Band) to afford the title compound as an off white solid. EI-MS m/z 410 (M+H). Calc'd for C21H23N5O2S: 409.16.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 10 h
  3. customwas brought to RT
  4. washwashed with saturated NH4Cl
  5. customThe organic phase was separated
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated by rotary evaporation
  9. custompurified by prep HPLC (Column Phenomenex type Prodigy 50 ODS3 100A size 250×21.20 mm 5u, Gradient 10% to 90% CH3CN:H2O containing 1% TFA over 20 min, Detector 254 nm, 4 nm Band)

Sources & evidence

ORD record
ord-dd372bf21bf244efbd9501ccc69c9536
Source dataset
uspto-grants-2003_11
Patent number
US06645990B2

Reaction notes

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