3-(Methylsulphonyl)aniline → HCID 90040870, compound

HRID 523021Notes

Reaction equation

HRID 523021 reaction equation
[C:1]([NH:5][C:6]([C:8]1[C:16]2[C:11](=[N:12][C:13]([CH3:18])=[C:14](Br)[N:15]=2)[N:10]([CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:26])([CH3:25])[CH3:24])[CH:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:27][S:28]([C:31]1[CH:32]=[C:33]([NH2:37])[CH:34]=[CH:35][CH:36]=1)(=[O:30])=[O:29].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.C(OCC)(=O)C.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]>[C:1]([NH:5][C:6]([C:8]1[C:16]2[C:11](=[N:12][C:13]([CH3:18])=[C:14]([NH:37][C:33]3[CH:34]=[CH:35][CH:36]=[C:31]([S:28]([CH3:27])(=[O:30])=[O:29])[CH:32]=3)[N:15]=2)[N:10]([CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:26])([CH3:25])[CH3:24])[CH:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 4280293-(Methylsulphonyl)anilineHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 90041146HCID 90041146, compound

Product 1

HCID 90040870HCID 90040870, compound

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 2-bromo-3-methyl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide (0.110 g, 0.25 mmol), 3-methanesulfonyl-phenylamine (0.086 g, 0.5 mmol), tris(dibenzylideneacetone)dipalladium (0.011 g, 0.0125 mmol), racemic BINAP [rac-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl](0.023 g, 0.038 mmol) and sodium tert-butoxide (0.060 g, 0.63 mmol) in toluene (2.5 mL), under an argon atmosphere, was heated and stirred in a sealed vessel at 110° C. for 21.5 h. The cooled reaction mixture was diluted with ethyl acetate, washed once with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. Purification by chromatography (silica, 75% ethyl acetate in hexanes) gave 0.107 g of slightly impure 2-(3-methanesulfonyl-phenylamino)-3-methyl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide as a yellow glass. The reaction was repeated as above, and the combined slightly impure products were purified further by chromatography (silica, 33% ethyl acetate in hexanes) to give 2-(3-methanesulfonyl-phenylamino)-3-methyl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide (0.169 g, 64%) as a light yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm −0.07 (s, 9H), 0.85 (t, J=8.2 Hz, 2H), 1.30 (s, 9H), 2.64 (s, 3H), 3.19 (s, 3H), 3.54 (t, J=8.2 Hz, 2H), 5.59 (s, 2H), 7.49 (m, 1H), 7.56 (m, 1H), 7.62 (s, 1H), 7.96 (m, 1H), 8.05 (m, 1H), 8.16 (s, 1H), 8.74 (s, 1H). MS (EI/CI) m/z: 532 [M+H].

Workup

  1. temperatureunder an argon atmosphere, was heated
  2. customThe cooled reaction mixture
  3. washwashed once with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customPurification by chromatography (silica, 75% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-b4c6a535bb814e5fb69920120a996d61
Source dataset
uspto-grants-2016_05
Patent number
US09334278B2

Reaction notes

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