2-Amino-4-methylpyridine → 3-(1-{5-[6(4-Methyl-pyridin-2-ylamino)pyridin-2-yl]thiazol-2-yl}piperidin-4-yl)propionic acid methyl ester

HRID 1716523Notes

Reaction equation

HRID 1716523 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.[CH3:55][O:56][C:57](=[O:78])[CH2:58][CH2:59][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.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[CH3:55][O:56][C:57](=[O:78])[CH2:58][CH2:59][CH:60]1[CH2:61][CH2:62][N:63]([C:66]2[S:67][C:68]([C:71]3[CH:76]=[CH:75][CH:74]=[C:73]([NH:47][C:48]4[CH:53]=[C:52]([CH3:54])[CH:51]=[CH:50][N:49]=4)[N:72]=3)=[CH:69][N:70]=2)[CH2:64][CH2:65]1

Participants

8

Reactant 4

HCID 15332-Amino-4-methylpyridineHCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 587064873-{1-[5-(6-Bromopyridin-2-yl)-thiazol-2-yl]piperidin-4-yl}propionic acid methyl ester

Product 1

HCID 587069463-(1-{5-[6(4-Methyl-pyridin-2-ylamino)pyridin-2-yl]thiazol-2-yl}piperidin-4-yl)propionic acid methyl esterYield 78.3%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

rac-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (91 mg, 0.15 mmol) and palladium acetate (25 mg, 0.11 mmol) were suspended in toluene (7 ml), and after 2-amino-4-picoline (79 mg, 0.73 mmol) and 3-{1-[5-(6-bromopyridin-2-yl)-thiazol-2-yl]piperidin-4-yl}propionic acid methyl ester (300 mg, 0.73 mmol) obtained in Step 2 were sequentially added, cesium carbonate (357 mg, 1.1 mmol) was added, and the mixture was stirred overnight at 100° C. Water was added to the reaction solution and the solution was 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 1:10) and the title compound (250 mg, 55%) was obtained.

Workup

  1. extractionthe solution was extracted 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 1:10)

Sources & evidence

ORD record
ord-55a059425f444a97aa47d6b13da1752b
Source dataset
uspto-grants-2010_09
Patent number
US07803801B2

Reaction notes

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