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

HRID 2095279노트

반응식

HRID 2095279 반응식
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

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 8028Tetrahydrofuran용매

실험 절차

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) 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).

후처리

  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)

출처 및 근거

ORD 기록
ord-b57b79a09eb24556905acf1e5a076b2d
출처 데이터셋
uspto-grants-2013_05
특허 번호
US08445679B2

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