Sodium Carbonate → HCID 86715468、化合物

HRID 2284559

反応式

HRID 2284559 の反応式
[Cl:1][C:2]1[C:7]([C:8]2[CH:9]=[C:10]3[C:14](=C[CH:16]=2)[NH:13][N:12]=[CH:11]3)=[CH:6][CH:5]=[CH:4][N:3]=1.BrC1C=C2C=NN(C(OC(C)(C)C)=O)C2=[N:22]C=1.ClC1C(B2OC(C)(C)C(C)(C)O2)=CC=CN=1.C([O-])([O-])=O.[Na+].[Na+]>C1COCC1.CO.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.O1CCOCC1>[Cl:1][C:2]1[C:7]([C:8]2[CH:9]=[C:10]3[CH:11]=[N:12][NH:13][C:14]3=[N:22][CH:16]=2)=[CH:6][CH:5]=[CH:4][N:3]=1

参加物

8

反応物 4

HCID 10340Sodium CarbonateHCID 120670602-Chloropyridine-3-boronic acid pinacol esterHCID 50986454tert-Butyl 5-bromo-1H-pyrazolo[3,4-b]pyridine-1-carboxylateHCID 867154695-(2-chloropyridin-3-yl)-1H-indazole

生成物 1

HCID 86715468HCID 86715468、化合物

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒HCID 312751,4-Dioxane溶媒HCID 21899815MeOH tetrahydrofuran溶媒

実験手順

5-(2-chloropyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine was prepared in the similar to the preparation of 5-(2-chloropyridin-3-yl)-1H-indazole by heating the mixture of tert-butyl 5-bromo-1H-pyrazolo[3,4-b]pyridine-1-carboxylate (2.0 g, 6.7 mmol), 2-chloro-3-pyridine boronic acid pinacol ester (1.9 g, 8.0 mmol), Pd(PPh3)4 (770 mg, 67 mmol), 1,4-dioxane (40 mL) and 2M aq.Na2CO3 (9 mL, 18 mmol) under argon atmosphere. After 12 h, the reaction mixture was cooled to room temperature and concentrated. The crude concentrate was diluted with EtOAc/water (200 mL/100 mL), allowed to stir for 30 min and the heterogeneous solution was filtered. The filter cake was washed with EtOAc (200 mL) and water (75 mL) successively. The filter cake thus obtained was analyzed as the desired product (0.55 g) and dissolved in a mixture of THF/MeOH (2:1, 50 mL). The homogeneous solution was passed through a pad of Celite® and the filtrate concentrated to provide desired product as a crystalline solid (0.45 g). Organic layer from combined filtrates was separated, stirred with MgSO4/Celite® for 20 min and filtered. The filtrate was concentrated and subjected to flash silica gel column purification (Combiflash® companion System® with RediSep® silica gel column 12 g, 30-50-90EtOAC/hexanes eluting solvent gradient upon dry loading the sample by absorbing on silica gel) to obtain another 0.4 g of 5-(2-chloropyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine. Total yield: 52%. 1H NMR (DMSO-d6): δ 13.83 (s, 1H), 8.59 (d, 1H, J=2.0 Hz), 8.45 (dd, 1H, J=1.7 and 4.7 Hz), 8.36 (d, 1H, J=2.0 Hz), 8.21 (s, 1H), 8.00 (dd, 1H, J=1.7 and 7.7 Hz), 7.59 (dd, 1H, J=4.7 and 7.7 Hz).LCMS: rt5.20 min (A), purity 94%, MS (m/e) 231 (MH+).

後処理

  1. custom5-(2-chloropyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine was prepared in the
  2. temperatureby heating
  3. concentrationconcentrated
  4. concentrationThe crude concentrate
  5. additionwas diluted with EtOAc/water (200 mL/100 mL)
  6. filtrationthe heterogeneous solution was filtered
  7. washThe filter cake was washed with EtOAc (200 mL) and water (75 mL) successively
  8. customThe filter cake thus obtained
  9. concentrationthe filtrate concentrated

出典と根拠

ORDレコード
ord-a9ccdb6caa5047d2b7d6385d41d5960c
出典データセット
uspto-grants-2015_09
特許番号
US09145433B2

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