2-Methylpiperidine → HCID 58924819, compound

HRID 1990998Notes

Reaction equation

HRID 1990998 reaction equation
C(O[C:4]([C:6]1[N:7]=[C:8]([I:11])[S:9][CH:10]=1)=[O:5])C.BrC1SC=C(C(O)=O)N=1.[CH:21]1[CH:22]=[CH:23][C:24]2N(O)N=[N:27][C:25]=2[CH:26]=1.Cl.CN(C)CCCN=C=NCC.CC1CCCCN1>ClCCl.C(#N)C>[I:11][C:8]1[S:9][CH:10]=[C:6]([C:4]([N:27]2[CH2:23][CH2:22][CH2:21][CH2:26][CH:25]2[CH3:24])=[O:5])[N:7]=1

Participants

8

Reactant 5

HCID 79742-MethylpiperidineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27632092-Bromo-1,3-thiazole-4-carboxylic acidHCID 684727782-Iodo-thiazole-4-carboxylic acid ethyl ester

Product 1

HCID 58924819HCID 58924819, compoundYield 30%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of a mixture of 2-iodo-thiazole-4-carboxylic acid ethyl ester and 2-bromo-thiazole-4-carboxylic acid (from Step 2; 11.5 g), N,N-dimethylaminopyridine (11.2 g, 91.7 mmol), HOBT (10.0 g, 74.0 mmol), 1-(3-dimethylaminopropyl)-3-ethyl-carbodiimide hydrochloride (14.0 g, 73.0 mmol), and 2-methyl-piperidine (8 mL, 68.1 mol) in dry dichloromethane (150 mL) and dry acetonitrile (20 mL) was stirred at room temperature for 72 h. At this time, the reaction mixture was concentrated in vacuo. The resulting solution was diluted with dichloromethane (25 mL) and 1 N HCl (250 mL). The mixture was stirred for several hours at room temperature. At this time, the mixture was filtered and the solids were washed with dichloromethane (200 mL). The aqueous layer was extracted with dichloromethane (2×250 mL). The combined organic layers were washed with water (450 mL) and brine (450 mL). The organic layer was dried over MgSO4, filtered, concentrated in vacuo, and purified by flash column chromatography eluting with a gradient of ethyl acetate in hexanes to give (2-iodo-thiazol-4-yl)-(2-methyl-piperidin-1-yl)-methanone (8.1 g, 30% yield from 2-amino-thiazole-4-carboxylic acid ethyl ester hydrobromide).

Workup

  1. concentrationAt this time, the reaction mixture was concentrated in vacuo
  2. additionThe resulting solution was diluted with dichloromethane (25 mL) and 1 N HCl (250 mL)
  3. stirringThe mixture was stirred for several hours at room temperature
  4. filtrationAt this time, the mixture was filtered
  5. washthe solids were washed with dichloromethane (200 mL)
  6. extractionThe aqueous layer was extracted with dichloromethane (2×250 mL)
  7. washThe combined organic layers were washed with water (450 mL) and brine (450 mL)
  8. dry with materialThe organic layer was dried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. custompurified by flash column chromatography
  12. washeluting with a gradient of ethyl acetate in hexanes

Sources & evidence

ORD record
ord-924703f5d2d94ef3815743eff3f636d8
Source dataset
uspto-grants-2010_01
Patent number
US07645773B2

Reaction notes

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