1H-Indazole-6-boronic acid → 6-(1H-indazol-6-yl)-N-(1-isopropyl-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-amine

HRID 2091707ノート

反応式

HRID 2091707 の反応式
Br[C:2]1[N:3]=[C:4]([NH:11][C:12]2[CH:13]=[N:14][N:15]([CH:17]([CH3:19])[CH3:18])[CH:16]=2)[C:5]2[N:6]([CH:8]=[CH:9][N:10]=2)[CH:7]=1.[NH:20]1[C:28]2[C:23](=[CH:24][CH:25]=[C:26](B(O)O)[CH:27]=2)[CH:22]=[N:21]1>C(=O)([O-])[O-].[Na+].[Na+].O1CCOCC1.C(Cl)Cl.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>[NH:20]1[C:28]2[C:23](=[CH:24][CH:25]=[C:26]([C:2]3[N:3]=[C:4]([NH:11][C:12]4[CH:13]=[N:14][N:15]([CH:17]([CH3:19])[CH3:18])[CH:16]=4)[C:5]4[N:6]([CH:8]=[CH:9][N:10]=4)[CH:7]=3)[CH:27]=2)[CH:22]=[N:21]1

参加物

8

反応物 2

HCID 247286171H-Indazole-6-boronic acidHCID 866424656-bromo-N-(1-isopropyl-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-amine

生成物 1

HCID 462396696-(1H-indazol-6-yl)-N-(1-isopropyl-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-amine収率 39.1%

試薬・触媒・溶媒 5

HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒HCID 6344Dichloromethane溶媒HCID 10340Sodium Carbonate溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
135 °C

実験手順

A mixture of impure 6-bromo-N-(1-isopropyl-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-amine (4) (195 mg), from above, and 1H-indazol-6-ylboronic acid (159 mg, 0.650 mmol) in 1 M aqueous sodium carbonate (1.3 mL) and 1,4-dioxane (3.5 mL) was sparged with nitrogen while stirring for 5 min. Tetrakis(triphenylphosphine)palladium(0) (69 mg, 0.060 mmol) was then added and the resulting mixture heated under microwave irradiation at 135° C. for 30 min. After this time, the reaction was diluted with methylene chloride (30 mL) and water (20 mL), and filtered through diatomaceous earth. The filtrate layers were separated and the aqueous phase was extracted with a mixture of 9:1 methylene chloride/methanol (100 mL). The combined organic layers were concentrated under reduced pressure and the resulting residue was purified by chromatography (silica, gradient, methylene chloride to 8:2 methylene chloride/methanol), then trituration with acetonitrile to afford 6-(1H-indazol-6-yl)-N-(1-isopropyl-1H-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-amine (5) (85 mg, 35%) as a yellow solid: mp>250° C.; 1H NMR (300 MHz, DMSO-d6) δ 13.23 (s, 1H), 9.95 (s, 1H), 8.59 (s, 1H), 8.24 (s, 1H), 8.18 (s, 1H), 8.10 (s, 1H), 8.00 (s, 1H), 7.97 (d, J=1.2 Hz, 1H), 7.85 (d, J=8.7 Hz, 1H), 7.75 (dd, J=8.7, 1.2 Hz, 1H), 7.62 (s, 1H), 4.52 (m, 1H), 1.47 (d, J=6.6 Hz, 6H); ESI MS m/z 359.4 [M+H]+; HPLC, 5.37 min, >99% (AUC).

後処理

  1. filtrationfiltered through diatomaceous earth
  2. customThe filtrate layers were separated
  3. extractionthe aqueous phase was extracted with a mixture of 9:1 methylene chloride/methanol (100 mL)
  4. concentrationThe combined organic layers were concentrated under reduced pressure
  5. customthe resulting residue was purified by chromatography (silica, gradient, methylene chloride to 8:2 methylene chloride/methanol)

出典と根拠

ORDレコード
ord-755008746d6344cfbc7fe8fad3f8f9cd
出典データセット
uspto-grants-2013_05
特許番号
US08440667B2

反応ノート

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