Potassium Carbonate → Ethyl 4-{[(3-chlorophenyl)sulfonyl]amino}-6-methyl-2-(1H-pyrazol-4-yl)thieno[2,3-b]pyridine-5-carboxylate

HRID 573595ノート

反応式

HRID 573595 の反応式
Br[C:2]1[S:27][C:5]2=[N:6][C:7]([CH3:26])=[C:8]([C:21]([O:23][CH2:24][CH3:25])=[O:22])[C:9]([NH:10][S:11]([C:14]3[CH:19]=[CH:18][CH:17]=[C:16]([Cl:20])[CH:15]=3)(=[O:13])=[O:12])=[C:4]2[CH:3]=1.O(C([N:35]1[CH:39]=[C:38](B(O)O)[CH:37]=[N:36]1)=O)C(C)(C)C.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.CN(C=O)C.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>[Cl:20][C:16]1[CH:15]=[C:14]([S:11]([NH:10][C:9]2[C:8]([C:21]([O:23][CH2:24][CH3:25])=[O:22])=[C:7]([CH3:26])[N:6]=[C:5]3[S:27][C:2]([C:38]4[CH:39]=[N:35][NH:36][CH:37]=4)=[CH:3][C:4]=23)(=[O:13])=[O:12])[CH:19]=[CH:18][CH:17]=1

参加物

8

反応物 3

HCID 11430Potassium CarbonateHCID 441186751-tert-Butoxycarbonyl-1H-pyrazole-4-boronic acidHCID 68323811Ethyl 2-bromo-4-{[(3-chlorophenyl)sulfonyl]amino}-6-methylthieno[2,3-b]pyridine-5-carboxylate

生成物 1

HCID 68380155Ethyl 4-{[(3-chlorophenyl)sulfonyl]amino}-6-methyl-2-(1H-pyrazol-4-yl)thieno[2,3-b]pyridine-5-carboxylate

試薬・触媒・溶媒 4

HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

Alternatively, a mixture of ethyl 2-bromo-4-{[(3-chlorophenyl)sulfonyl]amino}-6-methylthieno[2,3-b]pyridine-5-carboxylate (Description 72) (8 g, 16.33 mmol), 1-tert-butoxylcarbonyl-1H-pyrazole-4-boronic acid, pinacol ester (9.61 g, 32.7 mmol), tetrakis(triphenylphosphine)palladium(0) (0.944 g, 0.817 mmol) and potassium carbonate (6.77 g, 49.0 mmol) in 1,4-dioxane (50 mL), DMF (25 mL) and water (12.5 mL) was heated at 100° C. for ca. 3 h. After cooling to RT, the reaction mixture was filtered through celite and the filtrate was concentrated. The residue was purified by chromatography on silica, eluting with a gradient of 0-100% ethyl acetate in DCM. The resulting material was then passed through an SCX cartridge, eluting with MeOH (ca. 200 mL) followed by 2M NH3 in MeOH (250 mL) and the basic methanolic fractions concentrated, to give the title compound (7.24 g). Some mixed fractions were further purified by MDAP (acidic conditions), to give the title compound (33 mg).

後処理

  1. temperatureAfter cooling to RT
  2. filtrationthe reaction mixture was filtered through celite
  3. concentrationthe filtrate was concentrated
  4. customThe residue was purified by chromatography on silica
  5. washeluting with a gradient of 0-100% ethyl acetate in DCM
  6. washeluting with MeOH (ca. 200 mL)
  7. concentrationthe basic methanolic fractions concentrated

出典と根拠

ORDレコード
ord-a4fc0776dda344c19913dd03a69a43dd
出典データセット
uspto-grants-2015_05
特許番号
US09029545B2

反応ノート

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