Sodium Carbonate → 1H-Indole-6-carboxamide

HRID 493973

反応式

HRID 493973 の反応式
Br[C:2]1[NH:3][C:4]2[C:9]([C:10]=1C1CCCCC1)=[CH:8][CH:7]=[C:6]([C:17]([NH:19]S(N(C)C)(=O)=O)=[O:18])[CH:5]=2.COC1C=CC(B(O)O)=C(C=O)C=1.[Li+].[Cl-].C([O-])([O-])=O.[Na+].[Na+]>CCO.C1(C)C=CC=CC=1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH:3]1[C:4]2[C:9](=[CH:8][CH:7]=[C:6]([C:17]([NH2:19])=[O:18])[CH:5]=2)[CH:10]=[CH:2]1

参加物

8

反応物 4

HCID 10340Sodium CarbonateHCID 433294Lithium ChlorideHCID 27343652-Formyl-4-methoxybenzeneboronic acidHCID 587651502-bromo-3-cyclohexyl-N-(dimethylsulfamoyl)-1H-indole-6-carboxamide

生成物 1

HCID 5948371H-Indole-6-carboxamide

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒HCID 21863594Toluene ethanol溶媒

反応条件

温度
70 °C

実験手順

To a slurried solution of 2-bromo-3-cyclohexyl-N-[(dimethylamino)sulfonyl]-indole-6-carboxamide (54.0 g, 126 mmol), 4-methoxy-2-formylphenylboronic acid (29.5 g, 164 mmol) and LiCl (13.3 g, 315 mmol) in EtOH/toluene (1:1, 1 L) was added a solution of Na2CO3 (40.1 g, 379 mmol) in water (380 mL). The reaction mixture was stirred 10 min. and then Pd(PPh3)4 (11.3 g, 10.0 mmol) was added. The reaction solution was flushed with nitrogen and heated at 70° C. (internal monitoring) overnight and then cooled to rt. The reaction was diluted with EtOAc (1 L) and EtOH (100 mL), washed carefully with IN aqueous HCl (1 L) and brine (500 mL), dried (MgSO4), filtered and concentrated. The residual solids were stirred with Et2O (600 mL) for 1 h and collected by filtration to yield 1H-indole-6-carboxamide, 3-cyclohexyl-N-[(dimethylamino)sulfonyl]-2-(2-formyl-4-methoxyphenyl)- (52.8 g, 109 mmol, 87%) as a yellow powder which was used without further purification. 1HNMR (300 MHz, d6-DMSO) δ 11.66 (s, 1H), 8.17 (s, 1H), 7.75 (d, J=8.4 Hz, 1H), 7.74 (d, J=8.4 Hz, 1H), 7.59 (dd, J=1.4, 8.4 Hz, 1H), 7.23-7.16 (m, 2H), 7.08 (dd, J=2.6, 8.4 Hz, 1H), 6.54 (d, J=8.8 Hz, 1H), 3.86 (s, 3H), 3.22-3.08 (m, 1H), 2.91 (s, 6H), 2.00-1.74 (m, 7H), 1.60-1.38 (m, 3H). 13CNMR (75 MHz, CDCl3) δ 165.7, 158.8, 147.2, 139.1, 134.3, 132.0, 123.4, 122.0, 119.2, 118.2, 114.8, 112.3, 110.4, 109.8, 79.6, 45.9, 37.2(2), 34.7, 32.0(2), 25.9(2), 24.9. LCMS: m/e 482 (M−H)−, ret time 2.56 min, column A, 4 minute gradient.

後処理

  1. customThe reaction solution was flushed with nitrogen
  2. temperaturecooled to rt
  3. additionThe reaction was diluted with EtOAc (1 L) and EtOH (100 mL)
  4. washwashed carefully with IN aqueous HCl (1 L) and brine (500 mL)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. stirringThe residual solids were stirred with Et2O (600 mL) for 1 h
  9. filtrationcollected by filtration

出典と根拠

ORDレコード
ord-9897cabb108c435f9e7e2d4b3ca740a8
出典データセット
uspto-grants-2009_05
特許番号
US07538103B2

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