1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 6-Chloro-n-((r)-3-{4-[(4-methoxy-phenyl)-(4-methyl-pyridin-3-ylmethyl)-amino]-piperidin-1-yl}-butyl)-2,4-dimethyl-nicotinamide

HRID 1782559Notes

Reaction equation

HRID 1782559 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].[Cl:29][C:30]1[CH:38]=[C:37]([CH3:39])[C:33]([C:34](O)=[O:35])=[C:32]([CH3:40])[N:31]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.CCN(C(C)C)C(C)C>CN(C=O)C.[Cl-].[Na+].O>[Cl:29][C:30]1[CH:38]=[C:37]([CH3:39])[C:33]([C:34]([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:35])=[C:32]([CH3:40])[N:31]=1

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 34465636-Chloro-2,4-dimethylnicotinic acidHCID 57562991HCID 57562991, compound

Product 1

HCID 159471196-Chloro-n-((r)-3-{4-[(4-methoxy-phenyl)-(4-methyl-pyridin-3-ylmethyl)-amino]-piperidin-1-yl}-butyl)-2,4-dimethyl-nicotinamideYield 80%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a solution of [1-((R)-3-amino-1-methyl-propyl)-piperidin-4-yl]-(4-methoxy-phenyl)-(4-methyl-pyridin-3-ylmethyl)-amine (63 mg, 0.17 mmol) in DMF (1.5 mL) was added 6-chloro-2,4-dimethyl-nicotinic acid (40 mg, 0.22 mmol), HOBT (31 mg, 0.23 mmol), EDCI (44 mg, 0.23 mmol) and DIPEA (85 μL, 0.50 mmol). After the mixture was stirred at room temperature overnight brine (5 mL) was added, and the mixture was extracted with CH2Cl2 (2×5 mL). The organic extracts were combined and dried (Na2SO4). After filtration the solvent was removed under vacuum, and the residue was purified by flash chromatography on a silica gel column (20:1:0.1, CH2Cl2/MeOH/NH4OH) to afford the title compound as a white solid (72 mg, 80%). 1H NMR (CDCl3) δ 0.98 (d, 3H, J=6.6 Hz), 1.00 (m, 1H), 1.19 (m, 1H), 1.54 (m, 1H), 1.71 (m, 1H), 1.80 (br d, 2H, J=12.6 Hz), 2.11 (t, 1H, J=11.2 Hz), 2.29 (s, 3H), 2.35 (s, 3H), 2.48 (t, 1H, J=11.2 Hz), 2.51 (s, 3H), 2.65-2.85 (m, 3H), 3.15-3.45 (m, 2H), 3.72 (s, 3H), 3.78 (m, 1H), 3.97 (s, 2H), 6.62-6.78 (m, 4H), 6.98 (s, 1H), 7.02 (d, 1H, J=4.8 Hz), 8.05 (br. S, 1H), 8.25 (s, 1H), 8.28 (d, 1H, J=5.1 Hz). 13C NMR (CDCl3) δ 13.74, 19.16, 19.22, 22.51, 30.07, 31.01, 31.72, 40.04, 44.27, 47.85, 52.20, 55.93, 59.41, 60.20, 114.75 (2C), 120.74 (2C), 122.85, 125.47, 132.90, 133.43, 142.69, 145.73, 147.66, 148.42, 149.78, 150.59, 154.22, 155.58, 167.68. ES-MS m/z 550 (M+H). Anal. Calcd. For C31H40N5ClO2.0.7CH2Cl2: C, 62.46; H, 6.85; N, 11.49. Found: C, 62.68; H, 6.89; N, 11.73.

Workup

  1. additionwas added
  2. extractionthe mixture was extracted with CH2Cl2 (2×5 mL)
  3. dry with materialdried (Na2SO4)
  4. filtrationAfter filtration the solvent
  5. customwas removed under vacuum
  6. customthe residue was purified by flash chromatography on a silica gel column (20:1:0.1, CH2Cl2/MeOH/NH4OH)

Sources & evidence

ORD record
ord-0f1ac2612a434355a73f01bff15bcbfa
Source dataset
uspto-grants-2009_03
Patent number
US07498346B2

Reaction notes

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