Triethylamine → HCID 66793408, compound

HRID 2069553Notes

Reaction equation

HRID 2069553 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][O:12]1)[N:6]=[CH:5]2.C(N(CC)CC)C.[CH2:24]([OH:28])[CH2:25][C:26]#[CH:27]>CCOC(C)=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[O:12]1[CH2:13][CH2:14][CH2:15][CH2:16][CH:11]1[N:7]1[C:8]2[C:4](=[CH:3][C:2]([C:27]#[C:26][CH2:25][CH2:24][OH:28])=[CH:10][CH:9]=2)[CH:5]=[N:6]1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 135663-Butyn-1-OLHCID 534338265-bromo-1-(oxan-2-yl)-1H-indazole2×

Product 1

HCID 66793408HCID 66793408, compoundYield 48.8%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of 5-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (17.0 g, 60.7 mmol; Intermediate 1), Pd(PPh3)2Cl2 (5.80 g, 6.07 mmol), CuI (1.20 g, 6.07 mmol), and triethylamine (170 mL) was added but-3-yn-1-ol (6.80 g, 97.2 mmol) under N2 atmosphere. The resulting mixture was stirred at 80° C. for 16 hours under N2 atmosphere. Upon completion, the reaction mixture was diluted with EtOAc and washed with water (3×50 mL). The organic layer was dried over Na2SO4 and concentrated in vacuo. The residue was purified by column chromatography on silica gel (30-50% EtOAc in petroleum ether) affording the title compound (8.0 g). 1H NMR (400 MHz, DMSO-d6): δ 8.09 (s, 1H), 7.83 (s, 1H), 7.70 (d, 1H), 7.40 (d, 1H), 5.84 (dd, 1H), 4.90 (br, 1H), 3.91-3.87 (m, 1H), 3.77-3.70 (m, 1H), 3.60 (t, 2H), 2.56 (t, 2H), 2.48-2.33 (m, 1H), 2.04-1.94 (m, 2H), 1.76-1.69 (m, 1H), 1.60-1.55 (m, 2H); LCMS: 271 (M+H)+.

Workup

  1. washwashed with water (3×50 mL)
  2. dry with materialThe organic layer was dried over Na2SO4
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by column chromatography on silica gel (30-50% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-840a6d47551b422f871da9febe764c4d
Source dataset
uspto-grants-2012_10
Patent number
US08299112B2

Reaction notes

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