4-[1-(2-aminopyrimidin-4-yl)-3-methyl-1H-indazol-6-yl]-2-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazol-2-yl)but-3-yn-2-ol → 4-[1-(2-aminopyrimidin-4-yl)-3-methyl-1H-indazol-6-yl]-2-(1H-imidazol-2-yl)but-3-yn-2-ol

HRID 1398564Notes

Reaction equation

HRID 1398564 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([C:17]#[C:18][C:19]([C:22]4[N:23](COCC[Si](C)(C)C)[CH:24]=[CH:25][N:26]=4)([OH:21])[CH3:20])[CH:15]=3)[C:10]([CH3:35])=[N:9]2)[CH:5]=[CH:4][N:3]=1>Cl.O1CCOCC1>[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([C:17]#[C:18][C:19]([C:22]4[NH:26][CH:25]=[CH:24][N:23]=4)([OH:21])[CH3:20])[CH:15]=3)[C:10]([CH3:35])=[N:9]2)[CH:5]=[CH:4][N:3]=1

Participants

4

Reactant 1

HCID 681816514-[1-(2-aminopyrimidin-4-yl)-3-methyl-1H-indazol-6-yl]-2-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazol-2-yl)but-3-yn-2-ol

Product 1

HCID 601636634-[1-(2-aminopyrimidin-4-yl)-3-methyl-1H-indazol-6-yl]-2-(1H-imidazol-2-yl)but-3-yn-2-ol

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of 4-[1-(2-aminopyrimidin-4-yl)-3-methyl-1H-indazol-6-yl]-2-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazol-2-yl)but-3-yn-2-ol in 4M HCl in dioxane (2.5 ml) was stirred at 40° C. for 2 h and then at 50° C. for a further 1 hr. The reaction mixture was then concentrated in vacuo and basified using saturated aqueous sodium bicarbonate solution. The product was extracted into DCM (2×3 mL) and the combined organics were washed with brine solution (2 ml), dried (Na2SO4), filtered and concentrated in vacuo. The crude product was purified by flash chromatography (Biotage, 5-12% methanol gradient in DCM) to give the title compound as an off-white solid: 1H NMR (500 MHz, DMSO) delta 1.90 (3H, s), 2.57 (3H, s), 6.42 (1H, s), 6.83 (1H, s), 6.96 (2H, s), 7.10-6.99 (2H, m), 7.35 (1H, d, J=8.2 Hz), 7.84 (1H, d, J=8.2 Hz), 8.25 (1H, d, J=5.5 Hz), 8.86 (1H, s), 12.01 (1H, s); LC-MS: m/z=+360.05 (M+H)+.

Workup

  1. concentrationThe reaction mixture was then concentrated in vacuo
  2. extractionThe product was extracted into DCM (2×3 mL)
  3. washthe combined organics were washed with brine solution (2 ml)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by flash chromatography (Biotage, 5-12% methanol gradient in DCM)

Sources & evidence

ORD record
ord-b49d5f06507b409080671b9f91b99be2
Source dataset
uspto-grants-2014_12
Patent number
US08901313B2

Reaction notes

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