Cesium fluoride → 7-(2-Chlorophenyl)-3-(3-(ethyl(1-naphthyl)amino)propyl)-1h-indole-2-carboxylic acid

HRID 2199752Notes

Reaction equation

HRID 2199752 reaction equation
Br[C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[NH:9][C:8]([C:11]([O:13]CC)=[O:12])=[C:7]2[CH2:16][CH2:17][CH2:18][N:19]([CH2:30][CH3:31])[C:20]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH:23]=[CH:22][CH:21]=1.[Cl:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=1B(O)O.F[B-](F)(F)F.C([PH+](C(C)(C)C)C(C)(C)C)(C)(C)C.[F-].[Cs+]>O1CCCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=1[C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[NH:9][C:8]([C:11]([OH:13])=[O:12])=[C:7]2[CH2:16][CH2:17][CH2:18][N:19]([CH2:30][CH3:31])[C:20]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH:23]=[CH:22][CH:21]=1

Participants

7

Reactant 4

HCID 25953Cesium fluorideHCID 27343222-Chlorophenylboronic acidHCID 2734635Tri-tert-butylphosphine tetrafluoroborateHCID 68938635Ethyl 7-bromo-3-(3-(ethyl(naphthalen-1-yl)amino)propyl)-1h-indole-2-carboxylate

Product 1

HCID 689371517-(2-Chlorophenyl)-3-(3-(ethyl(1-naphthyl)amino)propyl)-1h-indole-2-carboxylic acid

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of EXAMPLE 531B (192 mg) and 2-chlorophenylboronic acid (76 mg) in tetrahydrofuran (6 ml) was added tris(dibenzylideneacetone)dipalladium(0) (19 mg), tri-t-butyl-phosphonium tetrafluoroborate (12 mg) and cesium fluoride (200 mg). The mixture was purged with argon and stirred at room temperature for 24 hours. The mixture was diluted with ethyl acetate (200 mL) and washed with water, and brine and dried over Na2SO4. Concentration of the mixture and column purification of the crude material (5% ethyl acetate in hexane) provided the title compound. A portion of this material (50 mg) was dissolved in 1:1 tetrahydrofuran/methanol with a few drops of water and hydrolyzed with LiOH. Subsequent purification via RP HPLC afforded the title compound. 1H NMR (300 MHz, DMSO-d6) δ 10.80 (m, 1H), 8.27 (m, 1H), 7.90 (m, 1H), 7.55 (m, 1H), 7.53 (m, 1H), 7.42 (m, 3H), 7.34 (m, 3H), 7.21 (m, 2H), 7.03 (m, 1H), 6.98 (m, 2H), 3.21 (m, 4H), 3.08 (t, 2H), 1.79 (m, 2H), 0.96 (t, 3H).

Workup

  1. customThe mixture was purged with argon
  2. additionThe mixture was diluted with ethyl acetate (200 mL)
  3. washwashed with water, and brine
  4. dry with materialdried over Na2SO4
  5. customConcentration of the mixture and column purification of the crude material (5% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-8e83260701dd45ff9a7eea08cebc7625
Source dataset
uspto-grants-2016_06
Patent number
US09359296B2

Reaction notes

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