Cyclopropylboronic acid → tert-Butyl 4-(((5-cyclopropyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate

HRID 913838ノート

反応式

HRID 913838 の反応式
Br[C:2]1[CH:10]=[C:9]([CH2:11][O:12][CH2:13][C:14]2([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]2)[C:8]2[C:4](=[CH:5][N:6]([CH2:33][O:34][CH2:35][CH2:36][Si:37]([CH3:40])([CH3:39])[CH3:38])[N:7]=2)[CH:3]=1.[CH:41]1(B(O)O)[CH2:43][CH2:42]1>[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH:41]1([C:2]2[CH:10]=[C:9]([CH2:11][O:12][CH2:13][C:14]3([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)[CH2:15][CH2:16][N:17]([C:20]([O:22][C:23]([CH3:24])([CH3:26])[CH3:25])=[O:21])[CH2:18][CH2:19]3)[C:8]3[C:4](=[CH:5][N:6]([CH2:33][O:34][CH2:35][CH2:36][Si:37]([CH3:40])([CH3:38])[CH3:39])[N:7]=3)[CH:3]=2)[CH2:43][CH2:42]1

参加物

4

反応物 2

HCID 2760897Cyclopropylboronic acidHCID 57546228tert-butyl 4-(((5-bromo-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate

生成物 1

HCID 57546153tert-Butyl 4-(((5-cyclopropyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate

試薬・触媒・溶媒 1

HCID 11979704Tetrakis(triphenylphosphine)palladium触媒

反応条件

温度
100 °C

実験手順

tert-Butyl 4-(((5-bromo-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate (42 mg, 0.07 mmol), cyclopropyl boronic acid (17.2 mg, 0.2 mmol), and tetrakis(triphenylphosphine) palladium(0) (7.7 mg, 0.007 mmol) were combined in dry tetrahydrofran (2 mL) in a microwave tube and sealed. After flushing the mixture with nitrogen, 0.24 mL of a 1 N potassium hydroxide aqueous solution was introduced. The mixture was heated at 100° C. for 1 h via microwave. After cooling to room temperature, the reaction mixture was concentrated and purified by flash chromatography on silica gel to afford 34 mg (86%). 1H-NMR (CDCl3, 300 MHz) δ 7.86 (s, 1H), 7.32 (m, 1H), 7.14-7.23 (m, 5H), 6.94 (m, 1H), 5.32 (s, 2H), 4.65 (s, 2H), 3.61-3.85 (m, 2H), 3.39 (s, 2H), 3.32-3.38 (m, 2H), 2.95-3.02 (m, 2H), 2.06-2.11 (m, 2H), 1.93-1.96 (m, 1H), 1.71-1.80 (m, 2H), 1.39 (s, 9H), 0.92-0.97 (m, 2H), 0.64-0.78 (m, 4H), 0.13 (s, 9H). Mass spec.: 592.24 (MH)+.

後処理

  1. customsealed
  2. customAfter flushing the mixture with nitrogen, 0.24 mL of a 1 N potassium hydroxide aqueous solution
  3. additionwas introduced
  4. temperatureAfter cooling to room temperature
  5. concentrationthe reaction mixture was concentrated
  6. custompurified by flash chromatography on silica gel
  7. customto afford 34 mg (86%)

出典と根拠

ORDレコード
ord-080d2d9e416d4d149bd0ffc20f5db6da
出典データセット
uspto-grants-2011_09
特許番号
US08026257B2

反応ノート

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