Potassium Carbonate → 3-(3-((6-Amino-1-naphthyl)oxy)propyl)-7-(2-methylphenyl)-1h-indole-2-carboxylic acid

HRID 2095282Notes

Reaction equation

HRID 2095282 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8]([O:12][CH2:13][CH2:14][CH2:15][C:16]1[C:24]3[C:19](=[C:20](Br)[CH:21]=[CH:22][CH:23]=3)[NH:18][C:17]=1[C:26]([O:28]CC)=[O:27])=[CH:7][CH:6]=[CH:5]2.[C:31]1([CH3:40])[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=1B(O)O.C([O-])([O-])=O.[K+].[K+].CO.FC(F)(F)C(O)=O>C(COC)OC.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O.C(O)C>[NH2:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8]([O:12][CH2:13][CH2:14][CH2:15][C:16]1[C:24]3[C:19](=[C:20]([C:32]4[CH:33]=[CH:34][CH:35]=[CH:36][C:31]=4[CH3:40])[CH:21]=[CH:22][CH:23]=3)[NH:18][C:17]=1[C:26]([OH:28])=[O:27])=[CH:7][CH:6]=[CH:5]2

Participants

9

Reactant 4

HCID 11430Potassium CarbonateHCID 27332672-Methylphenyl boronic acidHCID 68938609ethyl 3-(3-(6-aminonaphthalen-1-yloxy)propyl)-7-bromo-1H-indole-2-carboxylateHCID 86669916Methanol trifluoroacetic acid

Product 1

HCID 251448913-(3-((6-Amino-1-naphthyl)oxy)propyl)-7-(2-methylphenyl)-1h-indole-2-carboxylic acid

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
160 °C

Procedure

A mixture of EXAMPLE 563A (45 mg), o-tolylboronic acid (15.7 mg), K2CO3 (1 M, 0.17 ml) and bis(triphenylphosphine)palladium(II) dichloride (7.2 mg, 0.01 mmol) in a mixture of dimethoxyethane (2.2 ml), ethanol (0.6 ml) and water (0.9 ml) was heated at 160° C. in a microwave reactor (CEM Discover) for 10 minutes. The reaction mixture was acidified with a diluted trifluoroacetic acid methanol solution and concentrated. The residue was suspended in a mixture of DMSO and methanol (1:1) and filtered. The filtrate was purified by RP HPLC to provide the desired product. 1H NMR (400 MHz, DMSO-D6) □ 10.43 (s, 1H), 8.08 (d, J=8.90 Hz, 1H), 7.69 (d, J=6.75 Hz, 1H), 7.31-7.34 (m, 2H), 7.18-7.29 (m, 5H), 7.02-7.11 (m, 5H), 6.64 (d, J=7.67 Hz, 1H), 4.15 (t, J=5.98 Hz, 2H), 2.49-2.53 (m, 2H), 2.17-2.25 (m, 2H), 2.06 (s, 3H).

Workup

  1. concentrationconcentrated
  2. additionThe residue was suspended in a mixture of DMSO and methanol (1:1)
  3. filtrationfiltered
  4. customThe filtrate was purified by RP HPLC

Sources & evidence

ORD record
ord-217357dbcc3447ba96b8a7f840c17536
Source dataset
uspto-grants-2013_05
Patent number
US08445679B2

Reaction notes

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