Piperidine → Piperidin-1-yl-[5-(tetrahydro-pyran-4-yl)-thiophen-3-yl]-methanone

HRID 1809050Notes

Reaction equation

HRID 1809050 reaction equation
[O:1]1[CH2:6][CH2:5][CH:4]([C:7]2[S:11][CH:10]=[C:9]([C:12]([OH:14])=O)[CH:8]=2)[CH2:3][CH2:2]1.CCN(C(C)C)C(C)C.CN(C(ON1N=N[C:34]2[CH:35]=[CH:36][CH:37]=[N:38][C:33]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.N1CCCCC1>CN(C=O)C>[N:38]1([C:12]([C:9]2[CH:8]=[C:7]([CH:4]3[CH2:3][CH2:2][O:1][CH2:6][CH2:5]3)[S:11][CH:10]=2)=[O:14])[CH2:33][CH2:34][CH2:35][CH2:36][CH2:37]1

Participants

6

Reactant 4

HCID 8082PiperidineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 595425925-(Tetrahydro-pyran-4-yl)-thiophene-3-carboxylic acid

Product 1

HCID 42644354Piperidin-1-yl-[5-(tetrahydro-pyran-4-yl)-thiophen-3-yl]-methanoneYield 53%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

5-(Tetrahydro-pyran-4-yl)-thiophene-3-carboxylic acid (0.107 g, 0.5 mmol) was dissolved in DMF (2 mL). DIPEA (1.0 mmol), HATU (0.5 mmol) and piperidine (0.5 mmol) were added and the reaction stirred at room temperature for 1 hour. The reaction was then partitioned between ethyl acetate and water and the organic solution separated and dried over magnesium sulphate, filtered and the solvent evaporated. The product was purified by HPLC, eluting with 40%-90% acetonitrile in water (0.1% formic acid) over 30 minutes. The fractions containing the desired product were concentrated under vacuum to give the title compound (74 mg). LCMS m/z 280.22 [M+H]+ RT=8.77 min (Analytical Method 1). 1H NMR δ (ppm)(CHCl3-d): 7.25 (s, 1H), 6.9 (t, 1H), 4.1-4.0 (m, 2H), 3.6 (m, 4H), 3.5 (m, 2H), 3.1-3.0 (m, 1H), 1.95-1.6 (m, 10H).

Workup

  1. customThe reaction was then partitioned between ethyl acetate and water
  2. customthe organic solution separated
  3. dry with materialdried over magnesium sulphate
  4. filtrationfiltered
  5. customthe solvent evaporated
  6. customThe product was purified by HPLC
  7. washeluting with 40%-90% acetonitrile in water (0.1% formic acid) over 30 minutes
  8. additionThe fractions containing the desired product
  9. concentrationwere concentrated under vacuum

Sources & evidence

ORD record
ord-a4ce60e552c6469da1cc457b658d1163
Source dataset
uspto-grants-2013_01
Patent number
US08362008B2

Reaction notes

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