Trifluoroacetic acid → HCID 53847737, compound

HRID 1584878Notes

Reaction equation

HRID 1584878 reaction equation
FC(F)(F)C(O)=O.[NH2:8][C:9]1[C:14]([C:15]([NH:17][CH2:18][CH:19]2[CH2:24][CH2:23][N:22]([C:25](OC(C)(C)C)=O)[CH2:21][CH2:20]2)=[O:16])=[CH:13][CH:12]=[CH:11][N:10]=1.C(=O)([O-])[O-].[K+].[K+].C1(C)C=CC(S(OC[C@@H:49]2[O:54][C:53]3[CH:55]=[C:56]([CH3:59])[CH:57]=[CH:58][C:52]=3[O:51][CH2:50]2)(=O)=O)=CC=1>ClCCl.C(#N)C>[NH2:8][C:9]1[C:14]([C:15]([NH:17][CH2:18][CH:19]2[CH2:20][CH2:21][N:22]([CH2:25][C@@H:49]3[O:54][C:53]4[CH:55]=[C:56]([CH3:59])[CH:57]=[CH:58][C:52]=4[O:51][CH2:50]3)[CH2:23][CH2:24]2)=[O:16])=[CH:13][CH:12]=[CH:11][N:10]=1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 186899742-amino-N-[(1-tert-butoxycarbonyl-4-piperidyl)methyl]pyridine-3-carboxamideHCID 53924546HCID 53924546, compound

Product 1

HCID 53847737HCID 53847737, compound

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolvent2×HCID 6344DichloromethaneSolvent

Procedure

Trifluoroacetic acid (5 ml) was added to a solution of 2-amino-N-[(1-tert-butoxycarbonyl-4-piperidyl)methyl]pyridine-3-carboxamide (0.92 g; prepared in a similar manner to that described in Example 2) in dichloromethane (10 ml) then the mixture stirred at ambient temperature for 2 hours and the solvent removed in vacuo. The crude 2-amino-N-(4-piperidylmethyl)pyridine-3-carboxamide trifluoroacetate thus produced was dissolved in anhydrous acetonitrile (10 ml) and potassium carbonate (1.5 g) was added, followed by a solution of (R)-7-methyl-1,4-benzodioxan-2-ylmethyl 4-toluenesulphonate (0.9 g) in anhydrous acetonitrile (5 ml). The mixture was heated under reflux for 18 hours then poured onto water and extracted with ether (2×100 ml). The combined extracts were washed with water then extracted with hydrochloric acid (1M; 50 ml). The acid extracts were washed with ether (100 ml) then basified with sodium hydrogen carbonate and extracted with ether (2×100 ml). These extracts were combined, washed with water and dried over magnesium sulphate. The solvent was evaporated and the residue purified by flash chromatography on silica eluting with a 20:1 mixture of dichloromethane and methanol. Appropriate fractions were combined and evaporated to give (S)-2-amino-N-{[1-(7-methyl-1,4-benzodioxan-2-ylmethyl)-4-piperidyl]methyl}pyridine-3-carboxamide as a colourless solid (0.36 g) m.p. 143-146° C., [α]D -46.23° (c=0.53, methanol).

Workup

  1. customprepared in a similar manner to that
  2. customthe solvent removed in vacuo
  3. customThe crude 2-amino-N-(4-piperidylmethyl)pyridine-3-carboxamide trifluoroacetate thus produced
  4. temperatureThe mixture was heated
  5. temperatureunder reflux for 18 hours
  6. additionthen poured onto water
  7. extractionextracted with ether (2×100 ml)
  8. washThe combined extracts were washed with water
  9. extractionthen extracted with hydrochloric acid (1M; 50 ml)
  10. washThe acid extracts were washed with ether (100 ml)
  11. extractionextracted with ether (2×100 ml)
  12. washwashed with water
  13. dry with materialdried over magnesium sulphate
  14. customThe solvent was evaporated
  15. customthe residue purified by flash chromatography on silica eluting with a 20:1 mixture of dichloromethane and methanol
  16. customevaporated

Sources & evidence

ORD record
ord-3303a453ac34477eb8daccdf98f48f53
Source dataset
uspto-grants-1999_08
Patent number
US05935973

Reaction notes

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