Sodium Carbonate → 5-(2-chloropyridin-3-yl)-1H-indazole

HRID 2284561

反応式

HRID 2284561 の反応式
Br[C:2]1[CH:10]=[C:9]2[C:5]([C:6](C(OC(C)(C)C)=O)=[N:7][NH:8]2)=[CH:4][CH:3]=1.[Cl:18][C:19]1[C:24](B2OC(C)(C)C(C)(C)O2)=[CH:23][CH:22]=[CH:21][N:20]=1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.C(Cl)Cl.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:18][C:19]1[C:24]([C:3]2[CH:4]=[C:5]3[C:9](=[CH:10][CH:2]=2)[NH:8][N:7]=[CH:6]3)=[CH:23][CH:22]=[CH:21][N:20]=1

参加物

7

反応物 3

HCID 10340Sodium CarbonateHCID 120670602-Chloropyridine-3-boronic acid pinacol esterHCID 667029121,1-Dimethylethyl 6-bromo-1H-indazole-3-carboxylate

生成物 1

HCID 867154695-(2-chloropyridin-3-yl)-1H-indazole収率 74.3%

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒HCID 6344Dichloromethane溶媒HCID 312751,4-Dioxane溶媒

実験手順

Analogous to the reaction conditions and work-up procedures used in the preparation of 5-(2-chloropyridin-3-yl)-1H-indazole, 5-(2-chloropyridin-3-yl)-1H-indazole was obtained by heating the mixture of tert-butyl 6-bromo-1H-indazole-carboxylate (7.3 g, 24.6 mmol), 2-chloro-3-pyridine boronic acid pinacol ester (7.0 g, 29.5 mmol), Pd(PPh3)4 (2 g, 1.7 mmol) and aq.Na2CO3 (44 mL, 88 mmol) in 1,4-dioxane (200 mL) under argon atmosphere. The crude concentrate that was obtained after the extractive work-up dissolved in CH2Cl2, adsorbed on to silica gel and dried. Subsequent purification by flash silica gel column chromatography (Combiflash® companion System® with RediSep® silica gel column 120 g, 30-70% EtOAC/hexanes eluting solvent gradient upon dry powder loading) provided 5-(2-chloropyridin-3-yl)-1H-indazole as a white solid (4.2 g, 74%). 1H NMR (DMSO-d6): δ 13.21 (s, 1H), 8.43 (dd, 1H, J=1.7 and 4.7 Hz), 8.12 (s, 1H), 7.93 (dd, 1H, J=1.7 and 7.6 Hz), 7.84 (d, 1H, J=8.5 Hz), 7.59 (s, 1H), 7.52 (dd, 1H, J=4.7 and 7.6 Hz), 7.17 (d, 1H, J=8.5 Hz).LCMS: rt 6.17 min (A), purity 98%, MS (m/e) 230 (MH+).

後処理

  1. temperatureby heating
  2. concentrationThe crude concentrate that
  3. customwas obtained after the extractive work-up
  4. customdried
  5. customSubsequent purification
  6. dry with materialby flash silica gel column chromatography (Combiflash® companion System® with RediSep® silica gel column 120 g, 30-70% EtOAC/hexanes eluting solvent gradient upon dry powder loading)

出典と根拠

ORDレコード
ord-b62aff9621ee4b3f8bdabf6bd19f8810
出典データセット
uspto-grants-2015_09
特許番号
US09145433B2

関連ノート

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