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

HRID 913838Notes

Reaction equation

HRID 913838 reaction equation
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

Participants

4

Reactant 2

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalyst

Conditions

Temperature
100 °C

Procedure

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)+.

Workup

  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%)

Sources & evidence

ORD record
ord-080d2d9e416d4d149bd0ffc20f5db6da
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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