Isopropylamine → N'-isopropyl-2,6-dimethyl-N-((R)-3-{4-[(4-methyl-pyridin-3-ylmethyl)-phenyl-amino]-piperidin-1-yl}-butyl)-terephthalamide

HRID 1782568Notes

Reaction equation

HRID 1782568 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([CH3:39])[C:10]=1[C:11]([NH:13][CH2:14][CH2:15][C@H:16]([N:18]1[CH2:23][CH2:22][CH:21]([N:24]([CH2:31][C:32]2[CH:33]=[N:34][CH:35]=[CH:36][C:37]=2[CH3:38])[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH2:20][CH2:19]1)[CH3:17])=[O:12])[C:5]([OH:7])=O.CCN=C=NCCCN(C)C.C1C=C[C:54]2N(O)N=[N:57][C:55]=2[CH:56]=1.C(N)(C)C.CCN(C(C)C)C(C)C>CN(C=O)C>[CH:55]([NH:57][C:5](=[O:7])[C:4]1[CH:8]=[C:9]([CH3:39])[C:10]([C:11]([NH:13][CH2:14][CH2:15][C@H:16]([N:18]2[CH2:23][CH2:22][CH:21]([N:24]([CH2:31][C:32]3[CH:33]=[N:34][CH:35]=[CH:36][C:37]=3[CH3:38])[C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[CH2:20][CH2:19]2)[CH3:17])=[O:12])=[C:2]([CH3:1])[CH:3]=1)([CH3:56])[CH3:54]

Participants

7

Reactant 5

HCID 6363IsopropylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 68969554HCID 68969554, compound

Product 1

HCID 44511873N'-isopropyl-2,6-dimethyl-N-((R)-3-{4-[(4-methyl-pyridin-3-ylmethyl)-phenyl-amino]-piperidin-1-yl}-butyl)-terephthalamideYield 19.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

3,5-Dimethyl-N-((R)-3-{4-[(4-methyl-pyridin-3-ylmethyl)-phenyl-amino]-piperidin-1-yl}-butyl)-terephthalamic acid (50.0 mg, 0.09 mmol), EDCI (19.9 mg, 0.10 mmol) and HOBT (14.1 mg, 0.10 mmol) were combined in DMF (4 mL) to give a pale yellow solution. To this solution was added isopropylamine (8.9 μL, 0.10 mmol) followed by DIPEA (19.7 μL, 0.11 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 preparative TLC (91:8:1, CH2Cl2/MeOH/NH4OH) afforded N′-isopropyl-2,6-dimethyl-N-((R)-3-{4-[(4-methyl-pyridin-3-ylmethyl)-phenyl-amino]-piperidin-1-yl}-butyl)-terephthalamide as a white foam (10.1 mg, 19%). 1H NMR (CDCl3) δ 1.02 (br s, 3H), 1.22 (d, 6H, J=7 Hz), 1.83 (m, 3H), 2.22 (m, 1H), 2.29 (s, 3H), 2.34 (s, 6H), 2.55 (m, 1H), 2.80 (m, 4H), 3.38 (m, 1H), 3.62 (m, 1H), 3.76 (m, 1H), 4.10 (s, 2H), 4.23 (sext, 1H, J=6 Hz), 6.04 (d, 1H, J=7 Hz), 6.59 (d, 2H, J=8 Hz), 6.72 (t, 1H, J=7 Hz), 7.05 (d, 1H, J=5 Hz), 7.16 (t, 2H, J=8 Hz), 7.34 (br s, 1H), 7.39 (s, 2H), 8.27 (s, 1H), 8.33 (d, 1H, J=5 Hz). ES-MS m/z 570 (M+H), 593 (M+Na). Anal. Calcd. For C35H47N5O2: C, 73.78; H, 8.31; N, 12.29.

Workup

  1. customto give a pale yellow solution
  2. customgave the crude product as a tan oil
  3. customPurification by preparative TLC (91:8:1, CH2Cl2/MeOH/NH4OH)

Sources & evidence

ORD record
ord-48e0b91def02474b9c6d4b1794f25246
Source dataset
uspto-grants-2009_03
Patent number
US07498346B2

Reaction notes

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