HCID 67343888, compound → HCID 67342451, compound

HRID 1846631Notes

Reaction equation

HRID 1846631 reaction equation
C(OC(=O)[NH:7][CH2:8][CH:9]1[CH2:14][CH2:13][N:12]([C:15]2[C:20]([NH:21][C:22](=[O:30])[C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([Cl:29])[CH:24]=3)=[CH:19][C:18]([S:31]([CH3:34])(=[O:33])=[O:32])=[CH:17][N:16]=2)[CH2:11][CH2:10]1)(C)(C)C>C(Cl)Cl.FC(F)(F)C(O)=O>[NH2:7][CH2:8][CH:9]1[CH2:10][CH2:11][N:12]([C:15]2[C:20]([NH:21][C:22](=[O:30])[C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([Cl:29])[CH:24]=3)=[CH:19][C:18]([S:31]([CH3:34])(=[O:32])=[O:33])=[CH:17][N:16]=2)[CH2:13][CH2:14]1

Participants

4

Reactant 1

HCID 67343888HCID 67343888, compound

Product 1

HCID 67342451HCID 67342451, compoundYield 85.3%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

A solution of 0.612 g (1.17 mmol) of [3′-(3-chloro-benzoylamino)-5′-methanesulfonyl-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-4-ylmethyl]-carbamic acid tert-butyl ester in a mixture of methylene chloride (2 mL) and trifluoroacetic acid (2 mL) is stirred for 3.5 hours in a capped flask. The reaction mixture is concentrated under reduced pressure, diluted with water, and washed with diethyl ether. The pH of the aqueous phase is adjusted to alkaline with an aqueous solution of sodium carbonate and extracted with ethyl acetate. The combined organic phase is washed with an aqueous solution of sodium carbonate followed by water then dried over anhydrous sodium sulfate and filtered to remove the drying agent. The aqueous phase is re-extracted with a 1:1 mixture of n-butanol:ethyl acetate followed by n-butanol. The organic phases from these extractions are washed with an aqueous solution of sodium carbonate followed by water. The organic phase is then concentrated under reduced pressure co-evaporating with toluene. The residue is dissolved in a mixture of methanol:methylene chloride, dried over anhydrous sodium sulfate and combined with the previous organic washings. The combined organic phase is concentrated under reduced pressure to give 0.422 g (85.0%) of N-(4-aminomethyl-5′-methanesulfonyl-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-3′-yl)-3-chloro-benzamide as a resin.

Workup

  1. concentrationThe reaction mixture is concentrated under reduced pressure
  2. additiondiluted with water
  3. washwashed with diethyl ether
  4. extractionextracted with ethyl acetate
  5. washThe combined organic phase is washed with an aqueous solution of sodium carbonate
  6. dry with materialthen dried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. customto remove the drying agent
  9. extractionThe aqueous phase is re-extracted with a 1:1 mixture of n-butanol
  10. extractionThe organic phases from these extractions
  11. washare washed with an aqueous solution of sodium carbonate
  12. concentrationThe organic phase is then concentrated under reduced pressure co-evaporating with toluene
  13. dissolutionThe residue is dissolved in a mixture of methanol
  14. dry with materialmethylene chloride, dried over anhydrous sodium sulfate
  15. concentrationThe combined organic phase is concentrated under reduced pressure

Sources & evidence

ORD record
ord-3e14c34352474ef5a1f7c1ad4e7fd418
Source dataset
uspto-grants-2015_02
Patent number
US08952004B2

Reaction notes

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