2-Amino-4-methylpyridine → 2-Methyl-2-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridin-2-yl]thiazol-2-yl}piperidin-4-yl)propionic acid ethyl ester

HRID 1716527Notes

Reaction equation

HRID 1716527 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](=[O:80])[C:59]([CH:62]1[CH2:67][CH2:66][N:65]([C:68]2[S:69][C:70]([C:73]3[CH:78]=[CH:77][CH:76]=[C:75](Br)[N:74]=3)=[CH:71][N:72]=2)[CH2:64][CH2:63]1)([CH3:61])[CH3:60])[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>[CH2:55]([O:57][C:58](=[O:80])[C:59]([CH3:61])([CH:62]1[CH2:63][CH2:64][N:65]([C:68]2[S:69][C:70]([C:73]3[CH:78]=[CH:77][CH:76]=[C:75]([NH:47][C:48]4[CH:53]=[C:52]([CH3:54])[CH:51]=[CH:50][N:49]=4)[N:74]=3)=[CH:71][N:72]=2)[CH2:66][CH2:67]1)[CH3:60])[CH3:56]

Participants

8

Reactant 4

HCID 15332-Amino-4-methylpyridineHCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 587068292-{1-[5-(6-Bromopyridin-2-yl)thiazol-2-yl]piperidin-4-yl}-2-methylpropionic acid ethyl ester

Product 1

HCID 587067352-Methyl-2-(1-{5-[6-(4-methylpyridin-2-ylamino)pyridin-2-yl]thiazol-2-yl}piperidin-4-yl)propionic acid ethyl esterYield 88%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

rac-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (213 mg, 0.34 mmol) and palladium acetate (58 mg, 0.26 mmol) were suspended in toluene (10 ml), and after 2-amino-4-picoline (203 mg, 1.88 mmol) and 2-{1-[5-(6-bromopyridin-2-yl)thiazol-2-yl]piperidin-4-yl}-2-methylpropionic acid ethyl ester (748 mg, 1.71 mmol) obtained in Step 2 were sequentially added, cesium carbonate (1.11 g, 3.41 mmol) was added, and the mixture was stirred overnight at 100° C. 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 chromatography on silica gel (n-hexane:ethyl acetate=1:1 to 1:3) and the title compound (697 mg, 88%) 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 chromatography on silica gel (n-hexane:ethyl acetate=1:1 to 1:3)

Sources & evidence

ORD record
ord-9c417abfd9234736988342c9e31799ea
Source dataset
uspto-grants-2010_09
Patent number
US07803801B2

Reaction notes

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