Piperidine → HCID 11454007, compound

HRID 2353352Notes

Reaction equation

HRID 2353352 reaction equation
[NH:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.CC(C)([O-])C.[K+].C([O:17][C:18](=[O:43])[CH2:19][CH2:20][NH:21][CH2:22][C:23]1[CH:42]=[CH:41][C:26]2[S:27][C:28]([C:30]3[CH:35]=[CH:34][C:33](Cl)=[C:32]([C:37]([F:40])([F:39])[F:38])[CH:31]=3)=[CH:29][C:25]=2[CH:24]=1)(C)(C)C>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[N:1]1([C:33]2[CH:34]=[CH:35][C:30]([C:28]3[S:27][C:26]4[CH:41]=[CH:42][C:23]([CH2:22][NH:21][CH2:20][CH2:19][C:18]([OH:43])=[O:17])=[CH:24][C:25]=4[CH:29]=3)=[CH:31][C:32]=2[C:37]([F:38])([F:40])[F:39])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 3

HCID 8082PiperidineHCID 23665647Potassium tert-butoxideHCID 68453320HCID 68453320, compound

Product 1

HCID 11454007HCID 11454007, compoundYield 28.8%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

Piperidine (30 μL, 2.0 mmol), Pd2 dba3 (2.7 mg, 0.003 mmol), potassium t-butoxide (59 mg, 0.53 mmol) and 1,3-bis-(2,6-diisopropylphenyl)-4,5-dihydroimidazol-2-ylidene HCl salt (2.6 mg, 0.006 mmol) are added sequentially to a solution of 3-{[2-(4-chloro-3-trifluoromethyl-phenyl)-benzo[b]thiophen-5-ylmethyl]-amino}-propionic acid tert-butyl ester (72 mg, 0.15 mmol) in 1,4-dioxane (0.8 mL). The mixture is irradiated in a microwave at 100° C. for 1 hour. The reaction is quenched with water and the mixture is concentrated in vacuo. The residue is dissolved in THF and aqueous 2N NaOH (4 mL, 1:1 v/v), and stirred at 60° C. for 3 hours. It is concentrated and purified with preparative LCMS to afford 20 mg of 3-{[2-(4-piperidin-1-yl-3-trifluoromethyl-phenyl)-benzo[b]thiophen-5-ylmethyl]-amino}-propionic acid, which is converted to HCl salt: 1H NMR (400 MHz, CD3OD) δ 8.15-8.00 (m, 4H), 7.87 (s, 1H), 7.63 (d, 1H), 7.57 (d, 1H), 4.48 (s, 2H), 3.44 (t, 2H), 3.03 (t, 4H), 2.89 (t, 2H), 1.90-1.80 (m, 4H), 1.75-1.65 (m, 2H); MS (ES) 463.4 (M+H+).

Workup

  1. customThe mixture is irradiated in a microwave at 100° C. for 1 hour
  2. customThe reaction is quenched with water
  3. concentrationthe mixture is concentrated in vacuo
  4. dissolutionThe residue is dissolved in THF
  5. concentrationIt is concentrated
  6. custompurified with preparative LCMS

Sources & evidence

ORD record
ord-0bb9587da47c4820aa8131c5605964a5
Source dataset
uspto-grants-2010_07
Patent number
US07750021B2

Reaction notes

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