Potassium Phosphate, Tribasic → 4-[[6-Chloro-5-[(cyclohexylacetyl)amino]-2-quinolinyl]methyl]-1-piperidinecarboxylic acid, 1,1-dimethylethyl ester

HRID 2217791Notes

Reaction equation

HRID 2217791 reaction equation
B1(B2C3CCCC2CCC3)C2CCCC1CCC2.[CH2:19]=[C:20]1[CH2:25][CH2:24][N:23]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:22][CH2:21]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].Cl[C:42]1[CH:51]=[CH:50][C:49]2[C:44](=[CH:45][CH:46]=[C:47]([Cl:62])[C:48]=2[NH:52][C:53](=[O:61])[CH2:54][CH:55]2[CH2:60][CH2:59][CH2:58][CH2:57][CH2:56]2)[N:43]=1>O.CN(C)C=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:62][C:47]1[C:48]([NH:52][C:53](=[O:61])[CH2:54][CH:55]2[CH2:56][CH2:57][CH2:58][CH2:59][CH2:60]2)=[C:49]2[C:44](=[CH:45][CH:46]=1)[N:43]=[C:42]([CH2:19][CH:20]1[CH2:25][CH2:24][N:23]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:22][CH2:21]1)[CH:51]=[CH:50]2

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 27568081-Boc-4-MethylenepiperidineHCID 113224419-Borabicyclo[3.3.1]nonane dimerHCID 86012996N-(2,6-Dichloro-5-quinolinyl)-cyclohexaneacetamide

Product 1

HCID 866097354-[[6-Chloro-5-[(cyclohexylacetyl)amino]-2-quinolinyl]methyl]-1-piperidinecarboxylic acid, 1,1-dimethylethyl ester

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

9-Borabicyclo[3.3.1]nonane dimer solution (3.5 mL, 2M in tetrahydrofuran) was added to 4-methylene-1-piperidinecarboxylic acid, 1,1-dimethylethyl ester (prepared according to the method of Journal of Medicinal Chemistry 2002, 45, 3143) (345 mg) at room temperature under nitrogen. The mixture was refluxed for 3 hours after which it was cooled to room temperature. Potassium phosphate (1 g) in water (1 mL) was added and the mixture stirred for 30 minutes. N-(2,6-Dichloro-5-quinolinyl)-cyclohexaneacetamide (Example 1 (a)) (300 mg) in N,N-dimethylformamide (2 mL) was added followed by tetrakis(triphenylphosphine)palladium(0) (20 mg). The reaction mixture was heated to 80-90° C. for 4 hours under nitrogen. On cooling to room temperature the reaction mixture was filtered through diatomaceous earth and the tetrahydrofuran removed under vacuum. The resulting mixture was poured into water and extracted with ethyl acetate. The combined organic extracts were dried, filtered and evaporated. Purification (SiO2, ethyl acetate:isohexane 20:80 as eluant) gave the sub-titled compound (200 mg).

Workup

  1. customprepared
  2. customat room temperature
  3. temperatureThe mixture was refluxed for 3 hours after which it
  4. temperatureThe reaction mixture was heated to 80-90° C. for 4 hours under nitrogen
  5. temperatureOn cooling to room temperature the reaction mixture
  6. filtrationwas filtered through diatomaceous earth
  7. customthe tetrahydrofuran removed under vacuum
  8. additionThe resulting mixture was poured into water
  9. extractionextracted with ethyl acetate
  10. customThe combined organic extracts were dried
  11. filtrationfiltered
  12. customevaporated
  13. customPurification (SiO2, ethyl acetate:isohexane 20:80 as eluant)

Sources & evidence

ORD record
ord-1aaa5d48b1184f1c9795c2447585b3f3
Source dataset
uspto-grants-2008_08
Patent number
US07408065B2

Reaction notes

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