2-Methyl-3-butyn-2-ol → HCID 60164278, compound

HRID 1398636Notes

Reaction equation

HRID 1398636 reaction equation
I[C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][N:8]2[C:11]2[N:16]=[CH:15][N:14]=[C:13]([NH:17][C:18]3[C:19]([O:24][CH3:25])=[N:20][CH:21]=[CH:22][CH:23]=3)[CH:12]=2)=[CH:4][CH:3]=1.C(N(CC)CC)C.[CH3:33][C:34]([OH:38])([C:36]#[CH:37])[CH3:35]>[Cu]I.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.C1COCC1>[CH3:25][O:24][C:19]1[C:18]([NH:17][C:13]2[N:14]=[CH:15][N:16]=[C:11]([N:8]3[C:9]4[C:5](=[CH:4][CH:3]=[C:2]([C:37]#[C:36][C:34]([CH3:35])([OH:38])[CH3:33])[CH:10]=4)[CH:6]=[N:7]3)[CH:12]=2)=[CH:23][CH:22]=[CH:21][N:20]=1

Participants

7

Reactant 3

HCID 82582-Methyl-3-butyn-2-olHCID 8471TriethylamineHCID 68181902HCID 68181902, compound

Product 1

HCID 60164278HCID 60164278, compound

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a pressure tube was added 6-(6-iodoindazol-1-yl)-N-(2-methoxypyridin-3-yl)pyrimidin-4-amine (120 mg, 0.27 mmol) followed by triethylamine (2 mL) and THF (2 mL). Next, copper(I) iodide (5.15 mg, 0.027 mmol), bis(triphenylphosphine)palladium(II) chloride (18.96 mg, 0.027 mmol) and 2-methylbut-3-yn-2-ol (0.05 ml, 0.54 mmol) were added and the reaction vessel was sealed and stirred at RT for 1 h. The reaction mixture was concentrated in vacuo and DCM (5 ml) was added. The organics were washed with 0.5M HCl (2×3 ml), water (3 ml) and brine (3 ml), and dried (Na2SO4), filtered and concentrated in vacuo. The crude product was purified by flash chromatography (Isolute column, 4:6 to 1:1 EtOAc:heptanes) to surrender the title compound as a white solid: 1H NMR (500 MHz, CDCl3) delta 1.69 (6H, s), 2.08 (1H, br. s.), 4.07 (3H, s), 6.99 (1H, dd, J=7.80, 4.97 Hz), 7.32-7.41 (2H, m), 7.69 (1H, d, J=8.20 Hz), 7.88 (1H, dd, J=4.97, 1.66 Hz), 8.19 (1H, s), 8.54-8.61 (1H, m), 8.77 (1H, s), 8.99 (1H, s); LC-MS: m/z=+401.10 (M+H)+.

Workup

  1. customthe reaction vessel was sealed
  2. concentrationThe reaction mixture was concentrated in vacuo and DCM (5 ml)
  3. additionwas added
  4. washThe organics were washed with 0.5M HCl (2×3 ml), water (3 ml) and brine (3 ml)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by flash chromatography (Isolute column, 4:6 to 1:1 EtOAc:heptanes)

Sources & evidence

ORD record
ord-45bcd458755b4283872d2185d2aaeb06
Source dataset
uspto-grants-2014_12
Patent number
US08901313B2

Reaction notes

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