1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 57588106, compound

HRID 1782566Notes

Reaction equation

HRID 1782566 reaction equation
[NH2:1][CH2:2][CH2:3][C@H:4]([N:6]1[CH2:11][CH2:10][CH:9]([N:12]([CH2:19][C:20]2[CH:21]=[N:22][CH:23]=[CH:24][C:25]=2[CH3:26])[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH2:8][CH2:7]1)[CH3:5].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[C:48]([C:50]1[CH:58]=[C:57]([CH3:59])[C:53]([C:54](O)=[O:55])=[C:52]([CH3:60])[CH:51]=1)#[N:49].CCN(C(C)C)C(C)C>CN(C=O)C>[C:48]([C:50]1[CH:58]=[C:57]([CH3:59])[C:53]([C:54]([NH:1][CH2:2][CH2:3][C@H:4]([N:6]2[CH2:7][CH2:8][CH:9]([N:12]([CH2:19][C:20]3[CH:21]=[N:22][CH:23]=[CH:24][C:25]=3[CH3:26])[C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[CH2:10][CH2:11]2)[CH3:5])=[O:55])=[C:52]([CH3:60])[CH:51]=1)#[N:49]

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 21336317HCID 21336317, compoundHCID 68973173HCID 68973173, compound

Product 1

HCID 57588106HCID 57588106, compoundYield 72%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

[1-((R)-3-Amino-1-methyl-propyl)-piperidin-4-yl]-(4-methyl-pyridin-3-ylmethyl)-phenyl-amine (200.0 mg, 0.57 mmol), EDCI (120.0 mg, 0.62 mmol) and HOBT (84.3 mg, 0.62 mmol) were combined in DMF (25 mL) to give a pale yellow solution. To this solution was added 4-cyano-2,6-dimethyl-benzoic acid (109.3 mg, 0.62 mmol) followed by DIPEA (119.0 μL, 0.68 mmol) and the resulting mixture was stirred at room temperature for 16 h. Standard workup according to General Procedure C gave the crude product as a tan oil. Purification by column chromatography on silica gel (97:2:1, CH2Cl2/MeOH/NH4OH) afforded 4-cyano-2,6-dimethyl-N-((R)-3-{4-[(4-methyl-pyridin-3-ylmethyl)-phenyl-amino]-piperidin-1-yl}-butyl)-benzamide as an off-white foam (209.0 mg, 72%). 1H NMR (CDCl3) δ 1.02 (d, 3H, J=6 Hz), 1.04 (m, 1H), 1.30 (m, 1H), 1.59 (m, 1H), 1.64 (s, 2H), 1.76 (m, 1H), 1.86 (m, 2H), 2.21 (t, 1H, J=11 Hz), 2.32 (s, 6H), 2.55 (t, 1H, J=11 Hz), 2.78 (m, 3H), 2.87 (s, 2H), 2.95 (s, 3H), 3.35 (m, 1H), 3.64 (m, 1H), 3.78 (sext, 1H, J=6 Hz), 4.07 (s, 2H), 6.59 (d, 2H, J=9 Hz), 6.73 (t, 1H, J=8 Hz), 7.14 (m, 3H), 7.50 (m, 1H), 8.01 (s, 1H), 8.28 (s, 1H), 8.35 (d, 1H, J=5 Hz).

Workup

  1. customto give a pale yellow solution
  2. customgave the crude product as a tan oil
  3. customPurification by column chromatography on silica gel (97:2:1, CH2Cl2/MeOH/NH4OH)

Sources & evidence

ORD record
ord-f17dc19cfefe40469c44c002235ae5f0
Source dataset
uspto-grants-2009_03
Patent number
US07498346B2

Reaction notes

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