2-(Piperidin-1-yl)aniline → 5-Cyano-1H-pyrrole-2-carboxylic Acid (2-piperidin-1-yl-phenyl)-amide

HRID 32885

Reaction equation

HRID 32885 reaction equation
[C:1]([C:3]1[NH:7][C:6]([C:8]([OH:10])=O)=[CH:5][CH:4]=1)#[N:2].Cl.CN(C)CCCN=C=NCC.OC1C2N=NNC=2C=CC=1.[N:33]1([C:39]2[CH:45]=[CH:44][CH:43]=[CH:42][C:40]=2[NH2:41])[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]1>ClCCl.[Cl-].[Na+].O>[N:33]1([C:39]2[CH:45]=[CH:44][CH:43]=[CH:42][C:40]=2[NH:41][C:8]([C:6]2[NH:7][C:3]([C:1]#[N:2])=[CH:4][CH:5]=2)=[O:10])[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]1

Participants

7

Reactant 4

HCID 4587952-(Piperidin-1-yl)anilineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 553027535-cyano-1H-pyrrole-2-carboxylic acidHCID 178418300HCID 178418300, compound

Product 1

HCID 116737515-Cyano-1H-pyrrole-2-carboxylic Acid (2-piperidin-1-yl-phenyl)-amideYield 45.3%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To 24.5 mg (0.180 mmol) 5-cyano-1H-pyrrole-2-carboxylic acid (as prepared in the previous step) in dichloromethane (10 mL) was added 53 mg (0.28 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI), hydroxybenzotriazole (HOBt, 30 mg, 0.22 mmol), and 2-piperidinoaniline (38 mg, 0.22 mmol) and the mixture stirred for 6.5 h at RT. The mixture was poured into brine (50 mL) and extracted with dichloromethane (3×20 mL). The organic layers were washed with brine (20 mL), dried over Na2SO4 and the solvent was removed in vacuo. Purification of the resulting residue by silica gel preparative TLC eluting with 30% ethyl acetate in hexane yielded 24 mg (42%) of the title compound as a brown solid. 1H-NMR (400 MHz, CDCl3): δ 11.90 and 10.45 (br s, 1H, rotomers), 9.60 and 9.38 (s, 1H, rotomers), 8.60 and 8.47 (d, 1H, J=7.9 Hz, rotomers), 7.29-6.74 (m, 5H), 2.85 (m, 4H), 1.78-1.68 (m, 6H). LC-MS (ESI, m/z): Calcd. for C17H19N4O, 295.2 (M+H); found: 295.2.

Workup

  1. extractionextracted with dichloromethane (3×20 mL)
  2. washThe organic layers were washed with brine (20 mL)
  3. dry with materialdried over Na2SO4
  4. customthe solvent was removed in vacuo
  5. customPurification of the resulting residue by silica gel preparative TLC
  6. washeluting with 30% ethyl acetate in hexane

Sources & evidence

ORD record
ord-d32e9458d66e40388d376036b40b4567
Source dataset
uspto-grants-2008_09
Patent number
US07427683B2

Linked notes

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