Nicotinic Acid → N-[3-(4-Cyclohexylcarbamoyl-piperidin-1-ylmethyl)-phenyl]-nicotinamide

HRID 1486717Notes

Reaction equation

HRID 1486717 reaction equation
[CH:1]1([NH:7][C:8]([CH:10]2[CH2:15][CH2:14][N:13]([CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([NH2:23])[CH:18]=3)[CH2:12][CH2:11]2)=[O:9])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[C:24](O)(=[O:31])[C:25]1[CH:30]=[CH:29][CH:28]=[N:27][CH:26]=1.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.CCN=C=NCCCN(C)C.Cl>C(Cl)Cl.CN(C1C=CN=CC=1)C>[CH:1]1([NH:7][C:8]([CH:10]2[CH2:11][CH2:12][N:13]([CH2:16][C:17]3[CH:18]=[C:19]([NH:23][C:24](=[O:31])[C:25]4[CH:30]=[CH:29][CH:28]=[N:27][CH:26]=4)[CH:20]=[CH:21][CH:22]=3)[CH2:14][CH2:15]2)=[O:9])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

8

Reactant 5

HCID 938Nicotinic AcidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 867065241-(3-Amino-benzyl)-piperidine-4-carboxylic acid cyclohexylamide

Product 1

HCID 129625936N-[3-(4-Cyclohexylcarbamoyl-piperidin-1-ylmethyl)-phenyl]-nicotinamide

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent3×

Procedure

To a solution of 1-(3-amino-benzyl)-piperidine-4-carboxylic acid cyclohexylamide BB-1 (200 mg, 0.57 mmol) in DCM (5 mL) are added successively nicotinic acid (70 mg, 0.57 mmol), HOBT (154 mg, 1.14 mmol), DMAP (14 mg, 0.11 mmol) and DIPEA (0.29 mL, 1.7 mmol). A solution of EDC hydrochloride (163 mg, 0.85 mmol) in DCM (2 mL) is added and the reaction mixture is stirred for 4 days at RT. The mixture is diluted with DCM (10 mL) and washed twice with sat.aq. NaHCO3 (20 mL). The combined organic phases are dried over MgSO4 and filtered. The solvent is evaporated under reduced pressure. The residue is dissolved in acetonitrile and purified by prep. HPLC E. LCMS C: tR=0.56 min; [M+H]+=421.4. 1H-NMR (DMSO-d6): δ 1.1-1.3 (m, 5H), 1.5-1.7 (m, 9H), 1.8-1.9 (m, 2H), 2.0-2.1 (m, 1H), 2.84 (d, J=9, 2H), 3.4-3.5 (m, 3H), 7.03 (d, J=7, 1H), 7.30 (t, J=7, 1H), 7.5-7.8 (m, 4H), 8.29 (d, J=8, 1H), 8.7-8.8 (m, 1H), 9.11 (s, 1H), 10.4 (s, 1H).

Workup

  1. washwashed twice with sat.aq
  2. dry with materialThe combined organic phases are dried over MgSO4
  3. filtrationfiltered
  4. customThe solvent is evaporated under reduced pressure
  5. dissolutionThe residue is dissolved in acetonitrile
  6. custompurified by prep

Sources & evidence

ORD record
ord-1edd147d5dd54c99b0b28283cbb29adc
Source dataset
uspto-grants-2016_08
Patent number
US09428456B2

Reaction notes

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