p-Toluenesulfonic acid → HCID 178433918, compound

HRID 1398558Notes

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:26]=[CH:25][N:24](C5CCCCO5)[N:23]=4)([OH:21])[CH3:20])[CH:15]=3)[C:10]([CH3:33])=[N:9]2)[CH:5]=[CH:4][N:3]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>CO>[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:26]=[CH:25][NH:24][N:23]=4)([OH:21])[CH3:20])[CH:15]=3)[C:10]([CH3:33])=[N:9]2)[CH:5]=[CH:4][N:3]=1

Participants

Conditions

Temperature: 55 °C

Procedure

To a solution of 4-[1-(2-aminopyrimidin-4-yl)-3-methylindazol-6-yl]-2-[1-(oxan-2-yl)-1,2,4-triazol-3-yl]but-3-yn-2-ol (60 mg, 0.13 mmol) in methanol (3 mL) was added p-toluenesulfonic acid (25.38 mg, 0.15 mmol). The reaction mixture was stirred at 55° C. for 1 hr, and then concentrated in vacuo. The crude residue was partitioned between saturated NaHCO3 solution (2 ml) and DCM (2×5 ml). The combined organic extracts were washed with brine (2 mL), dried (Na2SO4), filtered and concentrated in vacuo. The crude product was purified by flash chromatography (Isolute column, 2-10% methanol gradient in DCM) to give the title compound: 1H NMR (500 MHz, DMSO) delta 1.92 (3H, s), 2.58 (3H, s), 6.96 (2H, s), 7.05 (1H, d, J=5.5 Hz), 7.46-7.28 (1H, m), 7.85 (1H, d, J=8.2 Hz), 8.26 (1H, d, J=5.5 Hz), 8.86 (1H, s), 14.01 (1H, s); LC-MS: m/z=+361.05 (M+H)+.

Workup

concentrationconcentrated in vacuo
customThe crude residue was partitioned between saturated NaHCO3 solution (2 ml) and DCM (2×5 ml)
washThe combined organic extracts were washed with brine (2 mL)
dry with materialdried (Na2SO4)
filtrationfiltered
concentrationconcentrated in vacuo
customThe crude product was purified by flash chromatography (Isolute column, 2-10% methanol gradient in DCM)

Sources & evidence

ORD record: ord-8a8fa37bb1a94435afa60b815e7dcef6
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08901313B2

Reaction notes

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