Piperidine → Piperidine-1-carboxylic acid [2-(4-cyclopentyl-piperazin-1-yl)-pyridin-4-yl]-methyl-amide

HRID 272541Notes

Reaction equation

HRID 272541 reaction equation
Cl.[CH:2]1([N:7]2[CH2:12][CH2:11][N:10]([C:13]3[CH:18]=[C:17]([NH:19][CH3:20])[CH:16]=[CH:15][N:14]=3)[CH2:9][CH2:8]2)[CH2:6][CH2:5][CH2:4][CH2:3]1.O=C(Cl)[O:23][C:24](Cl)(Cl)Cl.CCN(CC)CC.[NH:36]1[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]1>C1COCC1>[CH:2]1([N:7]2[CH2:8][CH2:9][N:10]([C:13]3[CH:18]=[C:17]([N:19]([CH3:20])[C:24]([N:36]4[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]4)=[O:23])[CH:16]=[CH:15][N:14]=3)[CH2:11][CH2:12]2)[CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

6

Reactant 4

HCID 8082PiperidineHCID 8471TriethylamineHCID 10426DiphosgeneHCID 68942107[2-(4-Cyclopentyl-piperazin-1-yl)-pyridin-4-yl]-methyl-amine hydrochloride2×

Product 1

HCID 11689259Piperidine-1-carboxylic acid [2-(4-cyclopentyl-piperazin-1-yl)-pyridin-4-yl]-methyl-amideYield 52%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 20 mg (0.08 mmol) [2-(4-cyclopentyl-piperazin-1-yl)-pyridin-4-yl]-methyl-amine hydrochloride (intermediate 10), 46 mg (0.08 mmol) diphosgene and 31 mg (0.3 mmol) NEt3 in 1 ml THF was treated with 43 mg (0.5 mmol) piperidine (commercially available) and stirred for 30 min at room temperature. After evaporation of all volatiles the residue was taken up in methanol/DMF and subjected to preparative HPLC purification on reversed phase eluting with a gradient of acetonitrile/water (0.05% triethylamine). The combined product fractions were evaporated to dryness to yield 15 mg (52%) of the title compound as white solid. MS(m/e): 372.1 (MH+; 100%).

Workup

  1. customAfter evaporation of all volatiles the residue
  2. customsubjected to preparative HPLC purification on reversed phase
  3. washeluting with a gradient of acetonitrile/water (0.05% triethylamine)
  4. customThe combined product fractions were evaporated to dryness

Sources & evidence

ORD record
ord-b24bbf12078e45dca1489fb5cf28cd8a
Source dataset
uspto-grants-2008_11
Patent number
US07456175B2

Reaction notes

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