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

HRID 913802Notes

Reaction equation

HRID 913802 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.[C:41]([C:43]1[CH:48]=[CH:47][C:46](B(O)O)=[CH:45][CH:44]=1)#[N:42].O1CCCC1.[OH-].[K+]>[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.C(OCC)C>[C:41]([C:43]1[CH:48]=[CH:47][C:46]([C:2]2[CH:10]=[C:9]([CH2:11][O:12][CH2:13][C:14]3([C:27]4[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=4)[CH2:15][CH2:16][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:24])[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]([CH3:39])([CH3:40])[CH3:38])[N:7]=3)[CH:3]=2)=[CH:45][CH:44]=1)#[N:42]

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 14797Potassium HydroxideHCID 27343264-Cyanophenylboronic acidHCID 57546228tert-butyl 4-(((5-bromo-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate

Product 1

HCID 57545973tert-Butyl 4-(((5-(4-cyanophenyl)-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 3283Diethyl EtherSolvent

Conditions

Temperature
110 °C

Procedure

A microwave tube was charged with tert-butyl 4-(((5-bromo-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate (400 mg, 0.63 mmol), 4-cyanophenylboronic acid (280 mg, 1.90 mmol), and tetrakis(triphenylphosphine)-palladium(0) (36.6 mg, 0.032 mmol). The tube was flushed with nitrogen and treated with tetrahydrofuran (12 mL) and potassium hydroxide (1 M in water) (1.90 mL, 1.90 mmol). The tube was sealed and heated at 110° C. for 1 h via microwave. The reaction was cooled, poured into diethyl ether, washed with water (2×), then brine, dried over magnesium sulfate, and concentrated. Column chromatography (25%→32% EtOAc/Hex) gave 391 mg (94%) as an oil. 1H-NMR (CDCl3, 500 MHz) δ 8.16 (s, 1H), 7.76 (d, J=1.2 Hz, 1H), 7.71 (d, J=8.2 Hz, 2H), 7.61 (d, J=8.6 Hz, 2H), 7.40 (m, 2H), 7.31 (m, 3H), 7.19 (m, 1H), 5.70 (s, 2H), 4.92 (s, 2H), 3.73 (br, 2H), 3.63 (t, J=8.2 Hz, 2H), 3.59 (s, 2H), 3.06 (m, 2H), 2.22 (m, 2H), 1.94 (m, 2H), 1.40 (s, 9H), 0.94 (t, J=8.2 Hz, 2H), −0.03 (s, 9H); 13C-NMR (CDCl3, 126 MHz) δ 155.1, 146.8, 146.3, 143.2, 133.4, 132.6, 129.5, 128.5, 127.8, 127.4, 126.3, 123.8, 122.7, 122.6, 119.1, 118.1, 110.5, 82.0, 79.9, 79.4, 68.9, 67.7, 41.8, 40.3 (br), 32.2, 28.6, 17.9, −1.3.

Workup

  1. customThe tube was flushed with nitrogen
  2. customThe tube was sealed
  3. temperatureThe reaction was cooled
  4. washwashed with water (2×)
  5. dry with materialbrine, dried over magnesium sulfate
  6. concentrationconcentrated
  7. customColumn chromatography (25%→32% EtOAc/Hex) gave 391 mg (94%) as an oil

Sources & evidence

ORD record
ord-f2960f138a0f43dea74bf4414318cbe7
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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