Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1) → HCID 68181909, compound

HRID 1398595Notes

Reaction equation

HRID 1398595 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]([OH:34])([C:21]4[CH:25]=[C:24]([CH2:26][O:27]C5CCCCO5)[O:23][N:22]=4)[CH3:20])[CH:15]=3)[C:10]([C:35]([N:37]([CH3:39])[CH3:38])=[O:36])=[N:9]2)[CH:5]=[CH:4][N:3]=1.CC1C=CC(S([O-])(=O)=O)=CC=1.[NH+]1C=CC=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]([OH:34])([C:21]4[CH:25]=[C:24]([CH2:26][OH:27])[O:23][N:22]=4)[CH3:20])[CH:15]=3)[C:10]([C:35]([N:37]([CH3:39])[CH3:38])=[O:36])=[N:9]2)[CH:5]=[CH:4][N:3]=1

Participants

4

Reactant 2

HCID 466102Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1)2×HCID 68181994HCID 68181994, compound

Product 1

HCID 68181909HCID 68181909, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
55 °C

Procedure

A solution of 1-(2-aminopyrimidin-4-yl)-6-(3-hydroxy-3-{5-[(oxan-2-yloxy)methyl]-1,2-oxazol-3-yl}but-1-yn-1-yl)-N,N-dimethylindazole-3-carboxamide (110 mg, 0.21 mmol) and pyridinium 4-methylbenzenesulfonate (5.18 mg, 0.2 mmol) in methanol (3 mL) was stirred at 60° C. for 1 hr, and then at RT for 3 days. Additional pyridinium 4-methylbenzenesulfonate was then added (20 mg, 0.8 mmol) and the reaction stirred at 55° C. for 1 hr. The reaction mixture was concentrated in vacuo and then saturated aqueous NaHCO3 (3 ml) solution was added. The product was extracted into DCM (5 ml×2). The combined organics were washed with brine and dried (Na2SO4), filtered and concentrated in vacuo. The crude product was purified by flash chromatography (Isolute column). Elution with 3% methanol in DCM gave the title compound: 1H NMR (500 MHz, DMSO) delta 1.88 (3H, s), 3.12 (3H, s), 4.57 (2H, d, J 6.0), 5.67 (1H, t, J 6.1), 6.55 (1H, s), 6.66 (1H, s), 7.10 (1 H, d, J 5.5), 7.16 (2H, s), 7.43 (1H, d, J 8.4), 8.01 (1H, d, J 8.5), 8.35 (1H, d, J 5.5), 8.95 (1H, s); LC-MS m/z=+448.05 (M+H)+.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. additionsaturated aqueous NaHCO3 (3 ml) solution was added
  3. extractionThe product was extracted into DCM (5 ml×2)
  4. washThe combined organics were washed with brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by flash chromatography (Isolute column)
  9. washElution with 3% methanol in DCM

Sources & evidence

ORD record
ord-096516f06115498e87f76ea58e772b16
Source dataset
uspto-grants-2014_12
Patent number
US08901313B2

Reaction notes

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