Sodium Hydroxide → {4-[Bis-(3-methyl-pyridin-2-ylmethyl)-amino]-piperidin-1-yl}-pyridin-3-yl-methanone

HRID 1592547Notes

Reaction equation

HRID 1592547 reaction equation
[CH3:1][C:2]1[C:3]([CH2:8][N:9]([CH2:16][C:17]2[C:22]([CH3:23])=[CH:21][CH:20]=[CH:19][N:18]=2)[CH:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)=[N:4][CH:5]=[CH:6][CH:7]=1.Cl.[C:25](Cl)(=[O:32])[C:26]1[CH:31]=[CH:30][CH:29]=[N:28][CH:27]=1.CCN(C(C)C)C(C)C.[OH-].[Na+]>C1COCC1>[CH3:1][C:2]1[C:3]([CH2:8][N:9]([CH2:16][C:17]2[C:22]([CH3:23])=[CH:21][CH:20]=[CH:19][N:18]=2)[CH:10]2[CH2:15][CH2:14][N:13]([C:25]([C:26]3[CH:27]=[N:28][CH:29]=[CH:30][CH:31]=3)=[O:32])[CH2:12][CH2:11]2)=[N:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 14798Sodium HydroxideHCID 81531DiisopropylethylamineHCID 884383-Pyridinecarbonyl chloride, hydrochloride (1:1)HCID 58996965Bis-(3-methyl-pyridin-2-ylmethyl)-piperidin-4-yl-amine

Product 1

HCID 58997112{4-[Bis-(3-methyl-pyridin-2-ylmethyl)-amino]-piperidin-1-yl}-pyridin-3-yl-methanoneYield 86%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of COMPOUND 249 (65 mg, 0.21 mmol) in THF (2 mL) was added nicotinoyl chloride hydrochloride (60 mg, 0.34 mmol) followed by DIPEA (0.10 mL, 0.57 mmol). The resultant mixture was stirred at room temperature for 40 minutes. The mixture was treated with 1.0 N NaOH (5 mL) and extracted with CH2Cl2 (4×10 mL). The combined organic extracts were dried (Na2SO4) and concentrated under reduced pressure. Purification of the crude material by radial chromatography on silica gel (1 mm plate, 20:1:1 CH2Cl2-MeOH—NH4OH) provided 75 mg (86%) of COMPOUND 265 as a white solid. 1H NMR (CDCl3) δ 1.61-1.75 (m, 2H), 1.90-1.99 (m, 2H), 2.09 (s, 6H), 2.55-3.00 (m, 3H), 3.75-3.90 (m, 5H), 4.75-4.80 (m, 1H), 7.09 (dd, 2H, J=7.5, 4.8 Hz), 7.34-7.39 (m, 3H), 7.75 (dt, 1H, J=6.0, 1.8 Hz), 8.35 (d, 2H, J=4.8 Hz), 8.65 (s, 2H); ES-MS m/z 416 (M+H).

Workup

  1. extractionextracted with CH2Cl2 (4×10 mL)
  2. dry with materialThe combined organic extracts were dried (Na2SO4)
  3. concentrationconcentrated under reduced pressure
  4. customPurification of the crude material by radial chromatography on silica gel (1 mm plate, 20:1:1 CH2Cl2-MeOH—NH4OH)

Sources & evidence

ORD record
ord-e03a8e80d1f94cfbbeefbe97d43149e2
Source dataset
uspto-grants-2007_11
Patent number
US07291631B2

Reaction notes

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