Triethylamine → (2-Phenyl-piperidin-1-yl)-(5-piperidin-4-yl-thiophen-3-yl)methanone

HRID 1809060Notes

Reaction equation

HRID 1809060 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[S:15][CH:16]=[C:17]([C:19]([OH:21])=O)[CH:18]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.C(N(CC)CC)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[C:53]1([CH:59]2[CH2:64][CH2:63][CH2:62][CH2:61][NH:60]2)[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1>C(#N)C.FC(F)(F)C(O)=O.C(Cl)Cl>[C:53]1([CH:59]2[CH2:64][CH2:63][CH2:62][CH2:61][N:60]2[C:19]([C:17]2[CH:18]=[C:14]([CH:11]3[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]3)[S:15][CH:16]=2)=[O:21])[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 1030202-PhenylpiperidineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 595424805-(1-(Tert-butoxycarbonyl)piperidin-4-yl)thiophene-3-carboxylic acid

Product 1

HCID 42644832(2-Phenyl-piperidin-1-yl)-(5-piperidin-4-yl-thiophen-3-yl)methanoneYield 51.1%

Reagents, catalysts & solvents 3

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

4-(4-Carboxy-thiophen-2-yl)-piperidine-1-carboxylic acid t-butyl ester (0.1 g, 0.32 mmol) was dissolved in acetonitrile (2 mL). Triethylamine (0.96 mmol), HATU (0.35 mmol) and 2-phenylpiperidine (0.35 mmol) were added and the reaction stirred at room temperature for 5 hours. The mixture was purified by HPLC, eluting with 10%-98% acetonitrile in water (0.1% formic acid) over 30 minutes. The fractions containing the desired product were concentrated under vacuum to give an oil which was dissolved in trifluoroacetic acid (3 mL) and DCM (5 mL) and stirred for 3 hours. The solvent was evaporated and the residue was purified by flash chromatography on an SCX-2 cartridge, washing with acetonitrile, then methanol and then eluting with 2 M ammonia in methanol. The fractions containing the desired product were concentrated under vacuum to give the title compound (0.058 g). LCMS m/z 355.18 [M+H]+ RT=6.59 min (Analytical Method 2). 1H NMR (400 MHz, CHCl3-d): δ 7.4 (m, 2H), 7.25 (m, 4H), 6.9 (s, 1H), 3.2 (d, 2H), 2.9 (m, 2H), 2.7 (m, 2H), 2.6 (m, 3H), 2.4 (d, 1H), 2.1-1.8 (m, 3H), 1.8-1.4 (m, 6H).

Workup

  1. customThe mixture was purified by HPLC
  2. washeluting with 10%-98% acetonitrile in water (0.1% formic acid) over 30 minutes
  3. additionThe fractions containing the desired product
  4. concentrationwere concentrated under vacuum
  5. customto give an oil which
  6. customThe solvent was evaporated
  7. customthe residue was purified by flash chromatography on an SCX-2 cartridge
  8. washwashing with acetonitrile
  9. washmethanol and then eluting with 2 M ammonia in methanol
  10. additionThe fractions containing the desired product
  11. concentrationwere concentrated under vacuum

Sources & evidence

ORD record
ord-7240b186ddf44b2ebf810169b76d802a
Source dataset
uspto-grants-2013_01
Patent number
US08362008B2

Reaction notes

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