Triethylamine → HCID 117778861, compound

HRID 1527008Notes

Reaction equation

HRID 1527008 reaction equation
[CH3:1][C:2]1[N:3]([CH:14]([CH3:22])[C:15](=[O:21])[N:16]2[CH2:20][CH2:19][CH2:18][CH2:17]2)[C:4]2[C:9]([C:10]=1[C:11](O)=[O:12])=[CH:8][CH:7]=[CH:6][CH:5]=2.C1C=C2N=NN(O)C2=CC=1.N.Cl.CN(C)CCCN=C=NCC.C(N(CC)CC)C.[NH2:53][CH2:54][C:55]1[C:56]([OH:63])=[N:57][C:58]([CH3:62])=[CH:59][C:60]=1[CH3:61]>ClCCl>[CH3:61][C:60]1[CH:59]=[C:58]([CH3:62])[NH:57][C:56](=[O:63])[C:55]=1[CH2:54][NH:53][C:11]([C:10]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]([CH:14]([CH3:22])[C:15](=[O:21])[N:16]2[CH2:20][CH2:19][CH2:18][CH2:17]2)[C:2]=1[CH3:1])=[O:12]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 1131751H-Benzotriazole, 1-hydroxy-, ammonium salt (1:1)HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 89740157HCID 89740157, compoundHCID 178425242HCID 178425242, compound

Product 1

HCID 117778861HCID 117778861, compoundYield 70%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2-Methyl-1-(1-oxo-1-(pyrrolidin-1-yl)propan-2-yl)-1H-indole-3-carboxylic acid (90 mg, 0.30 mmol) was dissolved in dichloromethane (15 mL), and then N-hydroxybenzotrizole (0.45 mmol, 60 mg), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.45 mmol, 86 mg), and triethylamine (1.69 mmol, 2 ml) was added to the mixture. After the mixture was stirred at room temperature for 10 minutes, 3-(aminomethyl)-4,6-dimethylpyridin-2-ol (0.30 mol, 50 mg) was added. The mixture was stirred at room temperature for 18 hours. Then washed with water (20 mL), extracted with dichloromethane (20 mL). The organic layer was separated, and concentrated to give a residue and the residue was purified by column chromatography (silica gel, dichloromethane/methanol=15:1) to give N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-1-(1-oxo-1-(pyrrolidin-1-yl)propan-2-yl)-1H-indole-3-carboxamide (60 mg, 70%). LCMS (M+H+) m/z: calcd 434.23. found 434. HPLC Purity (214 nm): 99%. 1H NMR (300 MHz, DMSO-d6) δ 11.62 (s, 1H), 7.75-7.72 (m, 2H), 7.42 (d, J=5.7 Hz, 1H), 7.10-7.06 (m, 2H), 5.89 (s, 1H), 5.49-5.44 (m, 1H), 4.32-4.30 (m, 2H), 3.42-3.32 (m, 3H), 3.28-3.16 (m, 1H), 2.61 (s, 3H), 2.26 (s, 3H), 2.12 (m, 3H), 2.02-1.96 (m, 1H), 1.70-1.57 (m, 3H), 1.42 (d, J=5.1 Hz, 3H).

Workup

  1. stirringThe mixture was stirred at room temperature for 18 hours
  2. washThen washed with water (20 mL)
  3. extractionextracted with dichloromethane (20 mL)
  4. customThe organic layer was separated
  5. concentrationconcentrated
  6. customto give a residue
  7. customthe residue was purified by column chromatography (silica gel, dichloromethane/methanol=15:1)

Sources & evidence

ORD record
ord-bedf9650bb3b438fb2313db13ee03134
Source dataset
uspto-grants-2015_07
Patent number
US09085583B2

Reaction notes

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