Sodium Hydroxide → 5-(3-(6-(4-fluorophenyl)-pyrazin-2-yl)-1H-indol-5-yl)-1,3,4-oxadiazol-2-amine

HRID 634111Notes

Reaction equation

HRID 634111 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:13]=[C:12]([C:14]3[C:22]4[C:17](=[CH:18][CH:19]=[C:20]([C:23]5[O:27][C:26]([NH:28]CC6C=CC(OC)=CC=6)=[N:25][N:24]=5)[CH:21]=4)[N:16](S(C4C=CC(C)=CC=4)(=O)=O)[CH:15]=3)[CH:11]=[N:10][CH:9]=2)=[CH:4][CH:3]=1.FC1C=CC(C2N=C(C3C4C(=CC=C(C5OC(N)=NN=5)C=4)N(S(C4C=CC(C)=CC=4)(=O)=O)C=3)C=NC=2)=CC=1.[OH-].[Na+]>C(O)(C(F)(F)F)=O.O1CCOCC1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:13]=[C:12]([C:14]3[C:22]4[C:17](=[CH:18][CH:19]=[C:20]([C:23]5[O:27][C:26]([NH2:28])=[N:25][N:24]=5)[CH:21]=4)[NH:16][CH:15]=3)[CH:11]=[N:10][CH:9]=2)=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 683277945-(3-(6-(4-fluorophenyl)pyrazin-2-yl)-1-tosyl-1H-indol-5-yl)-N-(4-methoxybenzyl)-1,3,4-oxadiazol-2-amineHCID 683286895-(3-(6-(4-fluorophenyl)pyrazin-2-yl)-1-tosyl-1H-indol-5-yl)-1,3,4-oxadiazol-2-amine

Product 1

HCID 683282085-(3-(6-(4-fluorophenyl)-pyrazin-2-yl)-1H-indol-5-yl)-1,3,4-oxadiazol-2-amineYield 27.3%

Reagents, catalysts & solvents 2

HCID 6422Trifluoroacetic acidSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of 5-(3-(6-(4-fluorophenyl)pyrazin-2-yl)-1-tosyl-1H-indol-5-yl)-N-(4-methoxybenzyl)-1,3,4-oxadiazol-2-amine (200 mg, 0.309 mmol) in TFA (1 ml) was heated to 100° C. in microwave for 30 min. The mixture was cooled to RT and TFA was removed in vacuo to give the crude material (130 mg, 80%). MS (ESI, pos. ion) m/z: 527 (M+1). To a solution of crude 5-(3-(6-(4-fluorophenyl)pyrazin-2-yl)-1-tosyl-1H-indol-5-yl)-1,3,4-oxadiazol-2-amine (130 mg, 0.247 mmol) in p-dioxane (1.3 mL) was added aq 10% NaOH (0.65 mL). The mixture was heated at 100° C. for 2 h and quenched with ice cold H2O. The resulting precipitate was filtered and washed with H2O. The crude was recrystallized with 10% MeOH/CHCl3 to give 5-(3-(6-(4-fluorophenyl)-pyrazin-2-yl)-1H-indol-5-yl)-1,3,4-oxadiazol-2-amine (25 mg, 27.3%) as an off-yellow solid. MS (ESI, pos. ion) m/z: 374.0 (M+1); 1H-NMR (400 MHz, DMSO-d6): δ 12.11 (s, 1H), 9.17 (s, 1H), 9.06 (s, 1H), 9.00 (s, 1H), 8.53 (m, 1H), 8.37-8.34 (m, 2H), 8.75-8.73 (m, 1H), 7.64 (d, J=8 Hz, 1H), 7.49 (m, 2H), 7.12 (s, 2H).

Workup

  1. customTFA was removed in vacuo
  2. customto give the crude material (130 mg, 80%)
  3. temperatureThe mixture was heated at 100° C. for 2 h
  4. customquenched with ice cold H2O
  5. filtrationThe resulting precipitate was filtered
  6. washwashed with H2O
  7. customThe crude was recrystallized with 10% MeOH/CHCl3

Sources & evidence

ORD record
ord-835bc3094b2b4462ba10c88bd8743956
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

Loading…