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

HRID 251262Notes

Reaction equation

HRID 251262 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-ebf00ba3b0c0410990ac311c7b57ab6f
Source dataset
uspto-grants-2011_01
Patent number
US07863293B2

Reaction notes

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