Propargyl alcohol → HCID 66793182, compound

HRID 1254423Notes

Reaction equation

HRID 1254423 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.[CH2:17]([OH:20])[C:18]#[CH:19]>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.C(N(CC)CC)C>[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:19]#[C:18][CH2:17][OH:20])=[CH:10][CH:9]=2)[CH:5]=[N:6]1

Participants

6

Reactant 2

HCID 7859Propargyl alcoholHCID 534338265-bromo-1-(oxan-2-yl)-1H-indazole2×

Product 1

HCID 66793182HCID 66793182, compoundYield 86.6%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8471TriethylamineSolvent

Conditions

Temperature
80 °C

Procedure

A 500 mL three-necked round bottom flask was charged with 5-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (14.0 g, 50 mmol; Intermediate 1) and triethylamine (300 mL). The flask was degassed with 3 cycles of vacuum/N2, followed by the addition of Pd(PPh3)2Cl2 (3.5 g, 5 mmol) and CuI (0.95 g, 5 mmol) under N2 atmosphere. The flask was again degassed with 3 cycles of vacuum/N2. Prop-2-yn-1-ol (8.4 g, 150 mmol) was added via syringe and the reaction mixture was stirred at 80° C. for 16 hours. Upon completion, the solvent was evaporated. The residue was diluted with dichloromethane (400 mL), washed with water (3×200 mL) and brine (200 mL), dried over anhydrous sodium sulfate, and concentrated in vacuo. The residue was further purified on silica gel column (1:100-1:20 EtOAc/petroleum ether) affording the title compound (11.1 g). 1H NMR (400 MHz, DMSO-d6): δ 8.13 (s, 1H), 7.90 (s, 1H), 7.75 (d, 1H), 7.44 (d, 1H), 5.86 (dd, 1H), 5.33 (t, 1H), 4.33 (d, 2H), 3.89-3.86 (m, 1H), 3.79-3.73 (m, 1H), 2.45-2.35 (m, 1H), 2.05-1.95 (m, 2H), 1.80-1.70 (m, 1H), 1.60-1.56 (m, 2H); LCMS: 257 (M+H)+.

Workup

  1. customThe flask was degassed with 3 cycles of vacuum/N2
  2. customThe flask was again degassed with 3 cycles of vacuum/N2
  3. customUpon completion, the solvent was evaporated
  4. additionThe residue was diluted with dichloromethane (400 mL)
  5. washwashed with water (3×200 mL) and brine (200 mL)
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe residue was further purified on silica gel column (1:100-1:20 EtOAc/petroleum ether)

Sources & evidence

ORD record
ord-5e731b4f13de4908b4aaaf6bbdaa897f
Source dataset
uspto-grants-2013_06
Patent number
US08455534B2

Reaction notes

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