2-Amino-4-methylpyridine → Ethyl 1-{5-[6-(4-methylpyridin-2-ylamino)pyridin-2-yl]thiazol-2-yl}piperidine-4-carboxylate

HRID 1716504Notes

Reaction equation

HRID 1716504 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[NH2:47][C:48]1[CH:53]=[C:52]([CH3:54])[CH:51]=[CH:50][N:49]=1.[CH2:55]([O:57][C:58]([CH:60]1[CH2:65][CH2:64][N:63]([C:66]2[S:67][C:68]([C:71]3[CH:76]=[CH:75][CH:74]=[C:73](Br)[N:72]=3)=[CH:69][N:70]=2)[CH2:62][CH2:61]1)=[O:59])[CH3:56].C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[CH3:54][C:52]1[CH:51]=[CH:50][N:49]=[C:48]([NH:47][C:73]2[N:72]=[C:71]([C:68]3[S:67][C:66]([N:63]4[CH2:62][CH2:61][CH:60]([C:58]([O:57][CH2:55][CH3:56])=[O:59])[CH2:65][CH2:64]4)=[N:70][CH:69]=3)[CH:76]=[CH:75][CH:74]=2)[CH:53]=1

Participants

8

Reactant 4

HCID 15332-Amino-4-methylpyridineHCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 587071151-[5-(6-Bromopyridin-2-yl)thiazol-2-yl]piperidine-4-carboxylic acid ethyl ester

Product 1

HCID 58707158Ethyl 1-{5-[6-(4-methylpyridin-2-ylamino)pyridin-2-yl]thiazol-2-yl}piperidine-4-carboxylateYield 55.4%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolvent2×

Conditions

Temperature
100 °C

Procedure

rac-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (434 mg, 0.70 mmol) and palladium acetate (117 mg, 0.52 mmol) was dissolve in toluene (15 ml), and after 2-amino-4-picoline (395 mg, 3.65 mmol) and a toluene (15 ml) solution of ethyl 1-[5-(6-bromopyridin-2-yl)thiazol-2-yl]piperidine-4-carboxylate obtained by Step 2 (1.38 g, 3.48 mmol) were sequentially added, cesium carbonate (1.70 g, 5.22 mmol) was added and the mixture was stirred at 100° C. overnight. Water was added to the reaction solution and extracted with ethyl acetate and washed with a saturated brine. The organic layer was dried over anhydrous sodium sulfate and the residue obtained by vacuum concentration was purified by silica gel chromatography (n-hexane:ethyl acetate=1:1 to 1:10) and the title compound (817 mg, 55%) was obtained.

Workup

  1. extractionextracted with ethyl acetate
  2. washwashed with a saturated brine
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. customthe residue obtained by vacuum concentration
  5. customwas purified by silica gel chromatography (n-hexane:ethyl acetate=1:1 to 1:10)

Sources & evidence

ORD record
ord-d782f929d7bf4b63b47bfd239d07c0ad
Source dataset
uspto-grants-2010_09
Patent number
US07803801B2

Reaction notes

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