Sodium Hydroxide → 5-(3-(4-cyclopropylpyrimidin-2-yl)-1H-indol-5-yl)-N-(2,2,2-trifluoroethyl)-1,3,4-oxadiazol-2-amine

HRID 634227Notes

Reaction equation

HRID 634227 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][CH:15]=[C:16]([C:19]5[O:23][C:22]([NH:24][CH2:25][C:26]([F:29])([F:28])[F:27])=[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.[OH-].[Na+]>O1CCOCC1.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][CH:15]=[C:16]([C:19]5[O:23][C:22]([NH:24][CH2:25][C:26]([F:28])([F:29])[F: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 2

HCID 14798Sodium HydroxideHCID 683285315-(3-(4-cyclopropylpyrimidin-2-yl)-1-tosyl-1H-indol-5-yl)-N-(2,2,2-trifluoroethyl)-1,3,4-oxadiazol-2-amine

Product 1

HCID 665547275-(3-(4-cyclopropylpyrimidin-2-yl)-1H-indol-5-yl)-N-(2,2,2-trifluoroethyl)-1,3,4-oxadiazol-2-amineYield 22.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

5-(3-(4-Cyclopropylpyrimidin-2-yl)-1-tosyl-1H-indol-5-yl)-N-(2,2,2-trifluoroethyl)-1,3,4-oxadiazol-2-amine (117 mg, 0.211 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 (eluting with 0-8% MeOH in DCM) to give 5-(3-(4-cyclopropylpyrimidin-2-yl)-1H-indol-5-yl)-N-(2,2,2-trifluoroethyl)-1,3,4-oxadiazol-2-amine (19.1 mg, 0.048 mmol, 22.61%) as a pale yellow amorphous solid. MS (ESI, pos. ion) m/z: 401.1 (M+1). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.95 (br. s., 1H), 9.01 (s, 1H), 8.50-8.59 (m, 2H), 8.27 (d, J=2.3 Hz, 1H), 7.70 (dd, J=8.5, 1.5 Hz, 1H), 7.60 (d, J=8.4 Hz, 1H), 7.16 (d, J=5.3 Hz, 1H), 4.05-4.21 (m, 2H), 2.08-2.20 (m, 1H), 1.20-1.29 (m, 2H), 1.07-1.16 (m, 2H).

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 (eluting with 0-8% MeOH in DCM)

Sources & evidence

ORD record
ord-111a600e16364e3f96410eb7c4aea31c
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

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