Sodium Hydroxide → 5-(3-(4-cyclopropyl-2-pyrimidinyl)-6-fluoro-1H-indol-5-yl)-N-(1-methylethyl)-1,3,4-oxadiazol-2-amine

HRID 634304Notes

Reaction equation

HRID 634304 reaction equation
[CH:1]1([C:4]2[CH:9]=[CH:8][N:7]=[C:6]([C:10]3[C:18]4[C:13](=[CH:14][C:15]([F:28])=[C:16]([C:19]5[O:23][C:22]([NH:24][CH:25]([CH3:27])[CH3:26])=[N:21][N:20]=5)[CH:17]=4)[N:12](S(C4C=CC(C)=CC=4)(=O)=O)[CH:11]=3)[N:5]=2)[CH2:3][CH2:2]1.O1CCOCC1.[OH-].[Na+]>[Cl-].[Na+].O>[CH:1]1([C:4]2[CH:9]=[CH:8][N:7]=[C:6]([C:10]3[C:18]4[C:13](=[CH:14][C:15]([F:28])=[C:16]([C:19]5[O:23][C:22]([NH:24][CH:25]([CH3:26])[CH3:27])=[N:21][N:20]=5)[CH:17]=4)[NH:12][CH:11]=3)[N:5]=2)[CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 312751,4-DioxaneHCID 683288885-(3-(4-cyclopropylpyrimidin-2-yl)-6-fluoro-1-tosyl-1H-indol-5-yl)-N-isopropyl-1,3,4-oxadiazol-2-amine

Product 1

HCID 665548995-(3-(4-cyclopropyl-2-pyrimidinyl)-6-fluoro-1H-indol-5-yl)-N-(1-methylethyl)-1,3,4-oxadiazol-2-amineYield 29%

Reagents, catalysts & solvents 1

HCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
100 °C

Procedure

A 5 mL glass microwave tube was charged with 5-(3-(4-cyclopropylpyrimidin-2-yl)-6-fluoro-1-tosyl-1H-indol-5-yl)-N-isopropyl-1,3,4-oxadiazol-2-amine (180 mg, 0.338 mmol) and treated with dioxane (2 mL) and 1 N NaOH (1 mL) and heated at 100° C. for 10 min in the microwave. The reaction mixture was treated with brine and extracted with EtOAc (2×20 mL), concentrated and purified by reverse phase using a Gilson automated platform (Silicycle Silichrome XT C18 column; 30×150 mm, 5 μm, 10-95% 0.1% TFA/CH3CN in 0.1% TFA/water by volume over 10 min), then dried in a Genevac Series II Evaporator affording the title compound (48.2 mg, 0.098 mmol, 29.0% yield) as a yellow amorphous solid. LC-MS (ESI, pos. ion) m/z: 379.2 (M+1). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.93-12.03 (1H, m), 8.98 (1H, d, J=7.4 Hz), 8.59 (1H, d, J=5.1 Hz), 8.29 (1H, d, J=2.7 Hz), 7.85 (1H, d, J=7.4 Hz), 7.45 (1H, d, J=11.3 Hz), 7.21 (1H, d, J=5.3 Hz), 3.82 (1H, dq, J=13.2, 6.5 Hz), 2.13-2.22 (1H, m), 1.27 (6H, d, J=6.5 Hz), 1.20-1.25 (2H, m), 1.12-1.20 (2H, m). 19F NMR (377 MHz, DMSO-d6) δ ppm −74.90 (3F, s), −119.9 (1F, s).

Workup

  1. extractionextracted with EtOAc (2×20 mL)
  2. concentrationconcentrated
  3. custompurified by reverse phase
  4. customa Gilson automated platform (Silicycle Silichrome XT C18 column; 30×150 mm, 5 μm, 10-95% 0.1% TFA/CH3CN in 0.1% TFA/water by volume over 10 min)
  5. dry with materialdried in a Genevac Series II Evaporator

Sources & evidence

ORD record
ord-daed3087d10f4628b5263f4a18ae4d15
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

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