Sodium Hydroxide → 2-cyclopropyl-5-(3-(4-cyclopropylpyrimidin-2-yl)-1H-indol-5-yl)-1,3,4-oxadiazole

HRID 634202Notes

Reaction equation

HRID 634202 reaction equation
[CH:1]1([C:4]2[O:5][C:6]([C:9]3[CH:10]=[C:11]4[C:15](=[CH:16][CH:17]=3)[N:14](S(C3C=CC(C)=CC=3)(=O)=O)[CH:13]=[C:12]4[C:28]3[N:33]=[C:32]([CH:34]4[CH2:36][CH2:35]4)[CH:31]=[CH:30][N:29]=3)=[N:7][N:8]=2)[CH2:3][CH2:2]1.[OH-].[Na+]>O1CCOCC1.O>[CH:1]1([C:4]2[O:5][C:6]([C:9]3[CH:10]=[C:11]4[C:15](=[CH:16][CH:17]=3)[NH:14][CH:13]=[C:12]4[C:28]3[N:33]=[C:32]([CH:34]4[CH2:36][CH2:35]4)[CH:31]=[CH:30][N:29]=3)=[N:7][N:8]=2)[CH2:3][CH2:2]1

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 683281792-cyclopropyl-5-(3-(4-cyclopropylpyrimidin-2-yl)-1-tosyl-1H-indol-5-yl)-1,3,4-oxadiazole

Product 1

HCID 683281682-cyclopropyl-5-(3-(4-cyclopropylpyrimidin-2-yl)-1H-indol-5-yl)-1,3,4-oxadiazoleYield 35.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

2-Cyclopropyl-5-(3-(4-cyclopropylpyrimidin-2-yl)-1-tosyl-1H-indol-5-yl)-1,3,4-oxadiazole (78.6 mg, 0.158 mmol) in a 5 mL glass microwave tube, was suspended in dioxane (1.5 mL). The suspension was treated with NaOH 1.000 n (2 mL, 2.000 mmol) (Fluka Analytical). The tube was sealed and the contents were stirred and heated in an Initiator microwave reactor (Personal Chemistry, Biotage AB, Inc., Upssala, Sweden) at 100° C. for 10 min. The mixture was diluted with H2O (10 mL) and extracted with EtOAc (2×25 mL). The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated. The crude material was purified by flash chromatography (0-10% MeOH in DCM) to give 2-cyclopropyl-5-(3-(4-cyclopropylpyrimidin-2-yl)-1H-indol-5-yl)-1,3,4-oxadiazole (19.2 mg, 0.056 mmol, 35.4%) as a pale yellow amorphous solid. MS (ESI, pos. ion) m/z: 344.0 (M+1). 1H NMR (400 MHz, DMSO-d6) ppm 11.99 (br. s., 1H), 9.10 (s, 1H), 8.56 (d, J=5.3 Hz, 1H), 8.28 (s, 1H), 7.77-7.84 (m, 1H), 7.62 (d, J=8.6 Hz, 1H), 7.20 (d, J=5.1 Hz, 1H), 2.29-2.38 (m, 1H), 2.09-2.20 (m, 1H), 1.12-1.33 (m, 8H).

Workup

  1. customThe tube was sealed
  2. extractionextracted with EtOAc (2×25 mL)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude material was purified by flash chromatography (0-10% MeOH in DCM)

Sources & evidence

ORD record
ord-65d96abcac6f4afab95c64eaf3930e7e
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

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