1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 44511970, compound

HRID 1782560Notes

Reaction equation

HRID 1782560 reaction equation
[NH2:1][CH2:2][CH2:3][C@H:4]([N:6]1[CH2:11][CH2:10][CH:9]([N:12]([C:21]2[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=2)[CH2:13][C:14]2[CH:15]=[N:16][CH:17]=[CH:18][C:19]=2[CH3:20])[CH2:8][CH2:7]1)[CH3:5].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[C:50]([C:52]1[CH:60]=[C:59]([CH3:61])[C:55]([C:56](O)=[O:57])=[C:54]([CH3:62])[CH:53]=1)#[N:51].CCN(C(C)C)C(C)C>CN(C=O)C>[C:50]([C:52]1[CH:60]=[C:59]([CH3:61])[C:55]([C:56]([NH:1][CH2:2][CH2:3][C@H:4]([N:6]2[CH2:7][CH2:8][CH:9]([N:12]([C:21]3[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=3)[CH2:13][C:14]3[CH:15]=[N:16][CH:17]=[CH:18][C:19]=3[CH3:20])[CH2:10][CH2:11]2)[CH3:5])=[O:57])=[C:54]([CH3:62])[CH:53]=1)#[N:51]

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 21336317HCID 21336317, compoundHCID 57562991HCID 57562991, compound

Product 1

HCID 44511970HCID 44511970, compoundYield 54.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

(R)-[1-(3-Amino-1-methyl-propyl)-piperidin-4-yl]-(4-methoxy-phenyl)-(4-methyl-pyridin-3-ylmethyl)-amine (1.00 g, 2.62 mmol), EDCI (0.55 g, 2.88 mmol) and HOBT (0.39 g, 2.88 mmol) were combined in DMF (5 mL) to give a pale yellow solution. To this solution was added 4-cyano-2,6-dimethyl-benzoic acid (0.50 g, 2.88 mmol) followed by DIPEA (1.14 mL, 6.55 mmol) and the resulting mixture was stirred at 25° C. 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 (CH2Cl2:MeOH:NH4OH, 96:3:1, v/v/v) afforded 4-cyano-N-((R)-3-{4-[(4-methoxy-phenyl)-(4-methyl-pyridin-3-ylmethyl)-amino]-piperidin-1-yl}-butyl)-2,6-dimethyl-benzamide (0.77 g, 54%) as a white foam. 1H NMR (CDCl3) δ 0.98-1.04 (d+m, 4H), 1.22 (m, 1H), 1.54 (m, 1H), 1.73-1.82 (m, 3H), 2.16 (t, 1H), 2.33 (s, 3H), 2.36 (s, 3H), 2.40 (m, 1H), 2.52 (m, 1H), 2.69-2.88 (m, 3H), 3.21 (m, 1H), 3.33 (m, 1H), 3.73 (s, 3H), 3.77 (m, 1H), 3.96 (s, 2H), 6.63 (d, 2H, J=9.0 Hz), 6.73 (d, 2H, J=9.0 Hz), 7.05 (d, 1H, J=6.0 Hz), 7.27 (s, 2H), 7.84 (br s, 1H), 8.25 (s, 1H), 8.31 (d, 1H, J=6.0 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 (CH2Cl2:MeOH:NH4OH, 96:3:1, v/v/v)

Sources & evidence

ORD record
ord-8b45e0d9f49947e4994e06da3272a1f0
Source dataset
uspto-grants-2009_03
Patent number
US07498346B2

Reaction notes

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