Triethylamine → N-((2-hydroxy-4,6-dimethylpyridin-3-yl)methyl)-4-isopropyl-2-methylbenzamide

HRID 2170457Notes

Reaction equation

HRID 2170457 reaction equation
[CH:1]([C:4]1[CH:12]=[CH:11][C:7]([C:8]([OH:10])=O)=[C:6]([CH3:13])[CH:5]=1)([CH3:3])[CH3:2].Cl.CN(C)CCCN=C=NCC.C(N(CC)CC)C.[NH2:33][CH2:34][C:35]1[C:36]([OH:43])=[N:37][C:38]([CH3:42])=[CH:39][C:40]=1[CH3:41]>ClCCl>[OH:43][C:36]1[C:35]([CH2:34][NH:33][C:8](=[O:10])[C:7]2[CH:11]=[CH:12][C:4]([CH:1]([CH3:2])[CH3:3])=[CH:5][C:6]=2[CH3:13])=[C:40]([CH3:41])[CH:39]=[C:38]([CH3:42])[N:37]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 224444172-Methyl-4-(1-methylethyl)benzoic acidHCID 178425242HCID 178425242, compound

Product 1

HCID 178425153N-((2-hydroxy-4,6-dimethylpyridin-3-yl)methyl)-4-isopropyl-2-methylbenzamideYield 36%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
20 °C

Procedure

To a solution of 4-isopropyl-2-methylbenzoic acid (80 mg, 0.45 mmol), 1-hydroxybenzotriozole (91 mg, 0.68 mmol), 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (130 mg, 0.68 mmol), triethylamine (0.3 mL) in dichloromethane (15 mL) was added 3-(aminomethyl)-4,6-dimethylpyridin-2-ol (69 mg, 0.45 mmol). The reaction mixture was stirred at 20° C. for 13 hours. The mixture was washed with water (20 mL×2). The organic phase was dried over sodium sulfate and filtered. The filtrate was concentrated. The residue was purified by column chromatography (silica gel, dichloromethane/methanol=10:1) to give N-((2-hydroxy-4,6-dimethylpyridin-3-yl)methyl)-4-isopropyl-2-methylbenzamide as a white solid (50 mg, 36%). LRMS (M+H+) m/z: calcd 312.18. found 312. HPLC Purity (214 nm): 99%. 1H NMR (300 MHz, d6-DMSO): δ 11.45 (s, 1H), 8.00 (t, J=4.8 Hz, 1H), 7.20-7.06 (m, 3H), 5.85 (s, 1H), 4.25 (d, J=4.8 Hz, 2H), 2.91-2.82 (m, 1H), 2.29 (s, 4H), 2.12 (s, 2H), 2.10 (s, 1H), 1.17 (m, 1H) (d, J=6.9 Hz, 6H).

Workup

  1. washThe mixture was washed with water (20 mL×2)
  2. dry with materialThe organic phase was dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationThe filtrate was concentrated
  5. customThe residue was purified by column chromatography (silica gel, dichloromethane/methanol=10:1)

Sources & evidence

ORD record
ord-0af208d1f794479182ede6716c4f1570
Source dataset
uspto-grants-2015_06
Patent number
US09051269B2

Reaction notes

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