Acetic Anhydride → N-(3-Hydroxymethyl-4-{[(3-methyl-pyridin-2-ylmethyl)-(1-pyridin-2-yl-ethyl)-amino]-methyl}-benzyl)-acetamide

HRID 1592669Notes

Reaction equation

HRID 1592669 reaction equation
[NH2:1][CH2:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:11][N:12]([CH2:21][C:22]2[C:27]([CH3:28])=[CH:26][CH:25]=[CH:24][N:23]=2)[C@H:13]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=2)[CH3:14])=[C:7]([CH2:9][OH:10])[CH:8]=1.[CH3:29][C:30](OC(C)=O)=[O:31].CCN(CC)CC.C([O-])(O)=O.[Na+]>C(Cl)Cl>[OH:10][CH2:9][C:7]1[CH:8]=[C:3]([CH:4]=[CH:5][C:6]=1[CH2:11][N:12]([CH2:21][C:22]1[C:27]([CH3:28])=[CH:26][CH:25]=[CH:24][N:23]=1)[CH:13]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=1)[CH3:14])[CH2:2][NH:1][C:30](=[O:31])[CH3:29]

Participants

6

Reactant 4

HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 67272526(S)-(5-aminomethyl-2-{[(3-methyl-pyridin-2-ylmethyl)-(1-pyridin-2-yl-ethyl)-amino]-methyl}-phenyl)-methanol

Product 1

HCID 67272807N-(3-Hydroxymethyl-4-{[(3-methyl-pyridin-2-ylmethyl)-(1-pyridin-2-yl-ethyl)-amino]-methyl}-benzyl)-acetamideYield 74.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (S)-(5-aminomethyl-2-{[(3-methyl-pyridin-2-ylmethyl)-(1-pyridin-2-yl-ethyl)-amino]-methyl}-phenyl)-methanol (0.0914 g, 0.24 mmol) in CH2Cl2 (3 mL) was added Ac2O (0.0228 mL, 0.24 mmol), Et3N (0.05 mL, 0.36 mmol>, and KI (0.0033 g, 0.02 mmol), and stirred at room temperature for 18 hours. Saturated NaHCO3 (10 mL) was added and extracted with CH2Cl2 (3×30 mL), and 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 0.0750 g (64%) of COMPOUND 401 as a white solid. 1H NMR (CDCl3) δ 1.55 (d, 3H, J=6.6 Hz), 1.71 (s, 2H), 1.99 (s, 3H), 2.05 (s, 3H), 3.63-3.77 (m, 2H), 3.81-3.96 (m, 2H), 4.02-4.09 (m, 1H), 4.20-4.29 (m, 2H), 4.37 (d, 2H, J=5.4 Hz), 5.76 (s, 1H), 6.87 (s, 1H), 7.04-7.23 (m, 3H), 7.33-7.39 (m, 2H), 7.66 (t, 1H, J=7.5 Hz), 8.38 (d, 2H, J=3.9 Hz), 8.57 (d, 2H, J=4.2 Hz). 13C NMR (CDCl3) δ 11.93, 18.45, 23.58, 43.70, 52.43, 53.86, 58.92, 63.32, 122.57, 122.67, 124.03, 127.44, 130.86, 132.10, 132.86, 136.70, 137.05, 138.55, 142.57, 146.56, 148.93, 156.59, 161.08, 170.41. ES-MS m/z 441.4 (M+Na). Anal. Calcd. for C25H30N4O2.0.8CH2Cl2.0.8H2O: C, 63.70; H, 6.55; N, 11.52. Found: C, 63.76; H, 6.56; N, 11.60.

Workup

  1. extractionextracted with CH2Cl2 (3×30 mL)
  2. dry with materialthe combined organic extracts were dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customPurification of the crude material by column chromatography on silica gel (50:1:1 CH2Cl2-MeOH—NH4OH)

Sources & evidence

ORD record
ord-023693aaaf1b4827a6dc3d3011f1f32f
Source dataset
uspto-grants-2007_11
Patent number
US07291631B2

Reaction notes

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