Trimethylamine → HCID 178425219, compound

HRID 1526952Notes

Reaction equation

HRID 1526952 reaction equation
[CH3:1][C:2]1[N:3]([CH:14]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH3:15])[C:4]2[C:9]([C:10]=1[C:11](O)=[O:12])=[CH:8][CH:7]=[CH:6][CH:5]=2.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.CN(C)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:11]([C:10]2[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[N:3]([CH:14]([C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=3)[CH3:15])[C:2]=2[CH3:1])=[O:12])=[C:55]([CH3:56])[CH:54]=[C:53]([CH3:57])[N:52]=1

Participants

8

Reactant 5

HCID 1146TrimethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 897404232-Methyl-1-(1-phenylethyl)-1H-indole-3-carboxylic acidHCID 178425242HCID 178425242, compound

Product 1

HCID 178425219HCID 178425219, compoundYield 59%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-methyl-1-(1-phenylethyl)-1H-indole-3-carboxylic acid (150 mg, 0.54 mmol) in anhydrous dichloromethane (10 mL) was added N-hydroxybenzotriazole (87 mg, 0.64 mmol), 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide hydrochloride (124 mg, 0.64 mmol) and trimethylamine (163 mg, 1.61 mmol). The mixture was stirred at room temperature for 0.5 hours, then 3-(aminomethyl)-4,6-dimethylpyridin-2-ol (98 mg, 0.64 mmol) was added. The mixture was stirred at room temperature for 12 hours. To the reaction mixture was added water (20 mL), extracted with dichloromethane (20 mL×2). The organic layers were combined and concentrated to give a residue. The residue was purified by column chromatography (silica gel, dichloromethane/methanol=20:1) to give compound N-((2-hydroxy-4,6-dimethylpyridin-3-yl)methyl)-2-methyl-1-(1-phenylethyl)-1H-indole-3-carboxamide as an off-white solid (130 mg, 59%). LRMS (M+H+) m/z: calcd 413.21. found 413. 1H NMR (300 MHz, d6-DMSO) δ: 11.59 (s, 1H), 7.73-7.66 (m, 2H), 7.34-7.29 (m, 3H), 7.23 (d, J=7.5 Hz, 1H), 7.16-6.89 (m, 4H), 5.94 (q, J=7.2 Hz, 1H), 5.88 (s, 1H), 4.32 (d, J=5.4 Hz, 2H), 2.60 (s, 3H), 2.27 (s, 3H), 2.11 (s, 3H), 1.88 (d, J=7.2 Hz, 3H).

Workup

  1. stirringThe mixture was stirred at room temperature for 12 hours
  2. extractionextracted with dichloromethane (20 mL×2)
  3. concentrationconcentrated
  4. customto give a residue
  5. customThe residue was purified by column chromatography (silica gel, dichloromethane/methanol=20:1)

Sources & evidence

ORD record
ord-0a518af959d1404a88a4e4160323e690
Source dataset
uspto-grants-2015_07
Patent number
US09085583B2

Reaction notes

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