Triethylamine → Methyl 3-[3-[3-[2-(4-chlorophenyl)-4-methylthiazol-5-yl]ureido]piperidin-1-yl]benzoate

HRID 602191Notes

Reaction equation

HRID 602191 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]([N:11]2[CH2:19][CH2:18][CH2:17][CH:13](C(O)=O)[CH2:12]2)[CH:8]=[CH:9][CH:10]=1)=[O:4].C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:27])C=CC=CC=1.C([N:39]([CH2:42]C)CC)C.[NH2:44][C:45]1[S:49][C:48]([C:50]2[CH:55]=[CH:54][C:53]([Cl:56])=[CH:52][CH:51]=2)=[N:47][C:46]=1[CH3:57]>C1C=CC=CC=1.O>[Cl:56][C:53]1[CH:54]=[CH:55][C:50]([C:48]2[S:49][C:45]([NH:44][C:42](=[O:27])[NH:39][CH:13]3[CH2:17][CH2:18][CH2:19][N:11]([C:7]4[CH:6]=[C:5]([CH:10]=[CH:9][CH:8]=4)[C:3]([O:2][CH3:1])=[O:4])[CH2:12]3)=[C:46]([CH3:57])[N:47]=2)=[CH:51][CH:52]=1

Participants

7

Reactant 4

HCID 8471Triethylamine2×HCID 199401P,P-Diphenylphosphinic azideHCID 589926191-[3-(Methoxycarbonyl)phenyl]nipecotic acidHCID 672673295-Amino-2-(4-chlorophenyl)-4-methylthiazole

Product 1

HCID 58992627Methyl 3-[3-[3-[2-(4-chlorophenyl)-4-methylthiazol-5-yl]ureido]piperidin-1-yl]benzoateYield 44%

Reagents, catalysts & solvents 2

HCID 241BenzeneSolventHCID 962WaterSolvent

Procedure

1-[3-(Methoxycarbonyl)phenyl]nipecotic acid (54.0 mg, 0.205 mmol) was suspended in benzene (4 mL). To this suspension, diphenylphosphoryl azide (0.0487 mL, 0.226 mmol) and triethylamine (0.0316 mL, 0.226 mmol) were added and the mixture was stirred for 2 hours while being refluxed. Subsequently, 5-amino-2-(4-chlorophenyl)-4-methylthiazole (46.0 mg, 0.205 mmol) and triethylamine (0.0316 mL, 0.226 mmol) were added and the mixture was further stirred for 6 hours while refluxed. Water was then added and the mixture was extracted with ethyl acetate. The extract was washed sequentially with 0.1 mol/L hydrochloric acid, a saturated aqueous sodium bicarbonate solution and brine. The washed product was dried over magnesium sulfate and the solvent was evaporated. Purification of the resulting residue by silica gel column chromatography (hexane:ethyl acetate=4:1->1:4) gave 43.5 mg (44%) of the desired compound as a yellow powder.

Workup

  1. temperaturewhile being refluxed
  2. stirringthe mixture was further stirred for 6 hours
  3. temperaturewhile refluxed
  4. extractionthe mixture was extracted with ethyl acetate
  5. washThe extract was washed sequentially with 0.1 mol/L hydrochloric acid
  6. dry with materialThe washed product was dried over magnesium sulfate
  7. customthe solvent was evaporated
  8. customPurification of the resulting residue by silica gel column chromatography (hexane:ethyl acetate=4:1->1:4)

Sources & evidence

ORD record
ord-2002cfafff2d46d2a42a0dfd9e64407f
Source dataset
uspto-grants-2011_03
Patent number
US07902367B2

Reaction notes

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