Triethylamine → HCID 178425196, compound

HRID 1500990Notes

Reaction equation

HRID 1500990 reaction equation
C[C:2]1[CH:10]=[C:9]([CH2:11][O:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.C(N(CC)CC)C.[NH2:48][CH2:49][C:50]1[C:51]([OH:58])=[N:52][C:53]([CH3:57])=[CH:54][C:55]=1[CH3:56]>ClCCl.O>[OH:58][C:51]1[C:50]([CH2:49][NH:48][C:4](=[O:6])[C:3]2[CH:2]=[CH:10][C:9]([CH2:11][O:12][C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=3)=[CH:8][CH:7]=2)=[C:55]([CH3:56])[CH:54]=[C:53]([CH3:57])[N:52]=1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 67601994Methyl 4-(phenoxymethyl)benzoic acidHCID 178425242HCID 178425242, compound

Product 1

HCID 178425196HCID 178425196, compoundYield 45%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of methyl 4-(phenoxymethyl)benzoic acid (420 mg, 1.84 mmol), 1-hydroxybenzotriazole (373 mg, 2.75 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (530 mg, 2.75 mmol), triethylamine (0.8 mL, 5.7 mmol) were dissolved in dichloromethane (20 mL). The mixture was stirred at room temperature for 0.5 hour. Then 3-(aminomethyl)-4,6-dimethylpyridin-2-ol (280 mg, 1.84 mmol) was added to the solution. The mixture was stirred at room temperature for 12 hours. To the resultant mixture, water (10 mL) was added and then extracted with dichloromethane (10 mL×3). The combined organic phase was separated, dried over sodium sulfate, filtered. The filtrate was concentrated in vacuo to give a residue. The residue was purified by column chromatography (silica gel, petroleum ether/ethyl acetate=1:4) to give N-((2-hydroxy-4,6-dimethylpyridin-3-yl)methyl)-4-(phenoxymethyl)benzamide (Compound I-11) as a white solid (300 mg, 45%). LRMS (M+H+) m/z: calcd 362.16. found 362. HPLC purity (214 nm): 98%. 1H NMR (300 MHz, d6-DMSO): δ 11.49 (s, 1H), 8.37 (t, J=5.1 Hz, 1H), 7.87 (d, J=8.4 Hz, 2H), 7.51 (d, J=8.4 Hz, 2H), 7.31 (t, J=7.8 Hz, 2H), 7.04-6.96 (m, 3H), 5.88 (s, 1H), 5.17 (s, 2H), 4.32 (d, J=5.1 Hz, 2H), 2.20 (s, 3H), 2.14 (s, 3H).

Workup

  1. stirringThe mixture was stirred at room temperature for 12 hours
  2. extractionextracted with dichloromethane (10 mL×3)
  3. customThe combined organic phase was separated
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated in vacuo
  7. customto give a residue
  8. customThe residue was purified by column chromatography (silica gel, petroleum ether/ethyl acetate=1:4)

Sources & evidence

ORD record
ord-42d33485956a40dd986f32a5490a4fc4
Source dataset
uspto-grants-2015_12
Patent number
US09206128B2

Reaction notes

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