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

HRID 913838노트

반응식

HRID 913838 반응식
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

참가 물질

4

반응물 2

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

생성물 1

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

시약·촉매·용매 1

HCID 11979704Tetrakis(triphenylphosphine)palladium촉매

반응 조건

온도
100 °C

실험 절차

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)+.

후처리

  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%)

출처 및 근거

ORD 기록
ord-080d2d9e416d4d149bd0ffc20f5db6da
출처 데이터셋
uspto-grants-2011_09
특허 번호
US08026257B2

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