2-Aminopyridine → HCID 58997035, compound

HRID 1592601Notes

Reaction equation

HRID 1592601 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-8645c4f5b0f3467ca72917e6ef6d72a8
Source dataset
uspto-grants-2007_11
Patent number
US07291631B2

Reaction notes

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