2-Aminopyridine → HCID 58997035, compound

HRID 251187Notes

Reaction equation

HRID 251187 reaction equation
[C:1]([N:8]1[CH:12]=[CH:11][N:10]=[CH:9]1)([N:3]1[CH:7]=[CH:6]N=[CH:4]1)=[O:2].N[C:14]1[CH:19]=CC=CN=1.CCN(C(C)C)C(C)C.[CH3:29][C:30]1[C:31]([CH2:36][N:37]([CH2:44][C:45]2[C:50]([CH3:51])=[CH:49][CH:48]=[CH:47][N:46]=2)[CH:38]2CCNC[CH2:39]2)=[N:32][CH:33]=[CH:34][CH:35]=1>C(Cl)Cl>[N:10]1[CH:11]=[CH:12][CH:19]=[CH:14][C:9]=1[NH:8][C:1]([N:3]1[CH2:4][CH2:39][CH:38]([N:37]([CH2:36][C:31]2[C:30]([CH3:29])=[CH:35][CH:34]=[CH:33][N:32]=2)[CH2:44][C:45]2[C:50]([CH3:51])=[CH:49][CH:48]=[CH:47][N:46]=2)[CH2:6][CH2:7]1)=[O:2]

Participants

6

Reactant 4

HCID 104392-AminopyridineHCID 682631,1'-CarbonyldiimidazoleHCID 81531Diisopropylethylamine2×HCID 58996965Bis-(3-methyl-pyridin-2-ylmethyl)-piperidin-4-yl-amine

Product 1

HCID 58997035HCID 58997035, compoundYield 51.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
60 °C

Procedure

A solution of 1,1′-carbonyldiimidazole (0.0924 g, 0.57 mmol), 2-aminopyridine (0.0489 g, 0.52 mmol), and DIPEA (0.18 mL, 1.04 mmol) in CH2Cl2 (6 mL) was stirred at room temperature for 4.5 hours. The mixture was concentrated, then dissolved in DMF (6 mL), and DIPEA (0.18 mL, 1.04 mmol) and COMPOUND 249 (0.1614 g, 0.52 mmol) were added. The mixture stirred at 60° C. for 20 hours, then concentrated. Saturated NaHCO3 (10 mL) was added and extracted with CH2Cl2 (3×40 mL). The combined organic extracts were dried (Na2SO4), filtered and concentrated. Purification of the crude material by column chromatography on silica gel (50:1:1 CH2Cl2-MeOH—NH4OH) provided 0.1148 g (46%) COMPOUND 344 as a white solid. 1H NMR (CDCl3) δ 1.61-1.74 (m, 2H), 1.95 (d, 2H, J=12.0 Hz), 2.07 (s, 6H), 2.68-2.77 (m, 3H), 3.80 (s, 4H), 4.17 (d, 2H, J=13.2 Hz), 6.88-6.92 (m, 1H), 7.05-7.09 (m, 2H), 7.35-7.37 (m, 2H), 7.58-7.65 (m, 2H), 7.98 (d, 1H, J=8.4 Hz), 8.17 (d, 1H, J=4.8 Hz), 8.32 (d, 2H, J=6.0 Hz). 13C NMR (CDCl3) 18.37, 27.49, 44.78, 54.96, 57.77, 113.67, 118.68, 122.36, 122.88, 133.82, 135.55, 138.51, 146.26, 147.82, 153.23, 154.14, 157.41. ES-MS m/z 431.3 (M+H). Anal. Calcd. for C25H30N6O.0.5H2O.0.6C3H4N2: C, 67.00; H, 7.01; N, 20.99. Found: C, 67.11; H, 6.94; N, 21.04.

Workup

  1. concentrationThe mixture was concentrated
  2. dissolutiondissolved in DMF (6 mL)
  3. concentrationconcentrated
  4. additionSaturated NaHCO3 (10 mL) was added
  5. extractionextracted with CH2Cl2 (3×40 mL)
  6. dry with materialThe combined organic extracts were dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification of the crude material by column chromatography on silica gel (50:1:1 CH2Cl2-MeOH—NH4OH)

Sources & evidence

ORD record
ord-8a3e653138f7489e8269009fad35596a
Source dataset
uspto-grants-2011_01
Patent number
US07863293B2

Reaction notes

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