Triethylamine → HCID 178425203, compound

HRID 1500984Notes

Reaction equation

HRID 1500984 reaction equation
[Br:1][C:2]1[CH:18]=[CH:17][CH:16]=[CH:15][C:3]=1[O:4][C:5]1[CH:13]=[CH:12][C:8]([C:9]([OH:11])=O)=[CH:7][C:6]=1[Cl:14].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>[Br:1][C:2]1[CH:18]=[CH:17][CH:16]=[CH:15][C:3]=1[O:4][C:5]1[CH:13]=[CH:12][C:8]([C:9]([NH:48][CH2:49][C:50]2[C:51]([OH:58])=[N:52][C:53]([CH3:57])=[CH:54][C:55]=2[CH3:56])=[O:11])=[CH:7][C:6]=1[Cl:14]

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 55223085HCID 55223085, compoundHCID 178425242HCID 178425242, compound

Product 1

HCID 178425203HCID 178425203, compoundYield 78%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

4-(2-Bromophenoxy)-3-chlorobenzoic acid (174 mg, 0.53 mmol), 1-hydroxybenzotriazole (108 mg, 0.8 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (154 mg, 0.8 mmol), triethylamine (0.4 mL, 2.88 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 (100 mg, 0.66 mmol) was added to the solution. The mixture was stirred at room temperature for 12 hours. To the mixture, water (20 mL) was added and the resultant mixture was extracted with dichloromethane (10 mL×3). The combined organic phase was separated, dried by sodium sulfate, filtered and concentrated to give a residue. The residue was purified by column chromatography (silica gel, dichloromethane/methanol=20:1) to give 4-(2-bromophenoxy)-3-chloro-N-((2-hydroxy-4,6-dimethylpyridin-3-yl)methyl)benzamide as a white solid (190 mg, 78%). LRMS (M+H) m/z: calcd 460.02. found 460. 1H NMR (300 MHz, d6-DMSO): δ 11.46 (s, 1H), 8.44 (t, J=4.5 Hz, 1H), 8.09 (d, J=1.8 Hz, 1H), 7.81-7.75 (m, 2H), 7.46-7.40 (m, 1H), 7.23-7.17 (m, 1H), 7.10 (dd, J=6.9 Hz, J=1.2 Hz, 1H), 6.83 (d, J=8.4 Hz, 1H), 5.85 (s, 1H), 4.27 (d, J=4.5 Hz, 2H), 2.15 (s, 3H), 2.10 (s, 3H).

Workup

  1. stirringThe mixture was stirred at room temperature for 12 hours
  2. extractionthe resultant mixture was extracted with dichloromethane (10 mL×3)
  3. customThe combined organic phase was separated
  4. dry with materialdried by sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give a residue
  8. customThe residue was purified by column chromatography (silica gel, dichloromethane/methanol=20:1)

Sources & evidence

ORD record
ord-ea0131efca274e9c8e71ac4067dd85fd
Source dataset
uspto-grants-2015_12
Patent number
US09206128B2

Reaction notes

Loading…