Triethylamine → 2-(4-(6-Bromo-1-(methylsulfonyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-1H-pyrazol-1-yl)-N,N-dimethylacetamide

HRID 2205912ノート

反応式

HRID 2205912 の反応式
[Br:1][C:2]1[CH:7]=[C:6]([NH:8][S:9]([CH3:12])(=[O:11])=[O:10])[C:5](I)=[CH:4][N:3]=1.[C:14]([C:16]1[CH:17]=[N:18][N:19]([CH2:21][C:22]([N:24]([CH3:26])[CH3:25])=[O:23])[CH:20]=1)#[CH:15].C(N(CC)CC)C>CN(C=O)C.C(OCC)(=O)C.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.[Cu](I)I>[Br:1][C:2]1[N:3]=[CH:4][C:5]2[CH:15]=[C:14]([C:16]3[CH:17]=[N:18][N:19]([CH2:21][C:22]([N:24]([CH3:26])[CH3:25])=[O:23])[CH:20]=3)[N:8]([S:9]([CH3:12])(=[O:11])=[O:10])[C:6]=2[CH:7]=1

参加物

8

反応物 3

HCID 8471TriethylamineHCID 86706267N-(2-Bromo-5-iodopyridin-4-yl)methanesulfonamideHCID 867063112-(4-Ethynyl-1H-pyrazol-1-yl)-N,N-dimethylacetamide

生成物 1

HCID 867063122-(4-(6-Bromo-1-(methylsulfonyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-1H-pyrazol-1-yl)-N,N-dimethylacetamide収率 88%

試薬・触媒・溶媒 4

HCID 83717Copper iodide触媒HCID 178418476HCID 178418476、化合物触媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
60 °C

実験手順

Bis(triphenylphosphine)palladiumdichloride (69 mg, 0.099 mmol) was added to a solution of N-(2-bromo-5-iodopyridin-4-yl)methanesulfonamide (Preparation 8, 0.5 g, 1.98 mmol), 2-(4-ethynyl-1H-pyrazol-1-yl)-N,N-dimethylacetamide (Preparation 101, 0.3 g, 1.7 mmol), triethylamine (1.05 g, 1.05 mmol) and copper iodide (19.5 mg, 0.098 mmol) in DMF (5 ml). The reaction mixture was heated for 1 hour at 60° C. The reaction was cooled to room temperature and diluted with ethyl acetate. The organic solution was washed with water, brine and dried over sodium sulphate. The solvent was removed in vacuum and the crude product purified on silica gel column chromatography eluting with a gradient of 10 to 20% methanol in ethyl acetate to afford the title compound as a white powder (0.3 g, 88%). 1H-NMR (500 MHz, d6-DMSO): δ 2.86 (s, 3H), 3.04 (s, 1H), 3.42 (s, 3H), 5.2 (s, 2H), 6.96 (s, 1H), 7.76 (s, 1H), 8.05 (s, 2H), 8.72 (s, 1H).

後処理

  1. temperatureThe reaction was cooled to room temperature
  2. washThe organic solution was washed with water, brine
  3. dry with materialdried over sodium sulphate
  4. customThe solvent was removed in vacuum
  5. customthe crude product purified on silica gel column chromatography
  6. washeluting with a gradient of 10 to 20% methanol in ethyl acetate

出典と根拠

ORDレコード
ord-8c593fc627784d9db2a793ed3b42157c
出典データセット
uspto-grants-2016_06
特許番号
US09371319B2

反応ノート

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