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

HRID 634113Notes

Reaction equation

HRID 634113 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:13]=[CH:12][N:11]=[C:10]([C:14]2[C:22]3[C:17](=[CH:18][CH:19]=[C:20]([C:23]4[O:27][C:26]([NH:28]CC5C=CC(OC)=CC=5)=[N:25][N:24]=4)[CH:21]=3)[N:16](S(C3C=CC(C)=CC=3)(=O)=O)[CH:15]=2)[N:9]=1.FC1C=CC=CC=1C1C=CN=C(C2C3C(=CC=C(C4OC(N)=NN=4)C=3)N(S(C3C=CC(C)=CC=3)(=O)=O)C=2)N=1.[OH-].[Na+]>C(O)(C(F)(F)F)=O.O1CCOCC1>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:13]=[CH:12][N:11]=[C:10]([C:14]2[C:22]3[C:17](=[CH:18][CH:19]=[C:20]([C:23]4[O:27][C:26]([NH2:28])=[N:25][N:24]=4)[CH:21]=3)[NH:16][CH:15]=2)[N:9]=1

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 683280085-(3-(4-(2-fluorophenyl)pyrimidin-2-yl)-1-tosyl-1H-indol-5-yl)-1,3,4-oxadiazol-2-amineHCID 683280415-(3-(4-(2-fluorophenyl)pyrimidin-2-yl)-1-tosyl-1H-indol-5-yl)-N-(4-methoxybenzyl)-1,3,4-oxadiazol-2-amine

Product 1

HCID 683283415-(3-(4-(2-fluorophenyl)pyrimidin-2-yl)-1H-indol-5-yl)-1,3,4-oxadiazol-2-amineYield 28.3%

Reagents, catalysts & solvents 2

HCID 6422Trifluoroacetic acidSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 5-(3-(4-(2-fluorophenyl)pyrimidin-2-yl)-1-tosyl-1H-indol-5-yl)-N-(4-methoxybenzyl)-1,3,4-oxadiazol-2-amine (250 mg, 0.38 mmol) in TFA (1.25 mL) was heated to 100° C. in a microwave for 30 min. The mixture was cooled to RT and TFA was removed in vacuo to give the crude material after washing with Et2O. MS (ESI, pos. ion) m/z: 527 (M+1). To a solution of crude 5-(3-(4-(2-fluorophenyl)pyrimidin-2-yl)-1-tosyl-1H-indol-5-yl)-1,3,4-oxadiazol-2-amine (250 mg, 0.47 mmol) in p-dioxane (2.5 mL) was added aq. 10% NaOH (1.25 mL) and the reaction was heated at 100° C. for 2 h. The reaction was quenched with ice cold H2O and the resulting precipitate was filtered, washed with ice cold H2O and dried. The crude product was recrystallized with 10% MeOH/CHCl3 to give 5-(3-(4-(2-fluorophenyl)pyrimidin-2-yl)-1H-indol-5-yl)-1,3,4-oxadiazol-2-amine (40 mg, 23%) as an off yellow solid. MS (ESI, pos. ion) m/z: 373.1 (M+1); 1H-NMR (400 MHz, DMSO-d6): δ 12.13 (s, 1H), 9.08 (s, 1H), 8.92 (m, 1H) 8.47 (d, J=2.8 Hz, 1H) 8.33-8.30 (m, 1H), 7.72-7.76 (m, 6H), 7.51-7.53 (m, 3H).

Workup

  1. customTFA was removed in vacuo
  2. customto give the crude material
  3. washafter washing with Et2O
  4. temperaturethe reaction was heated at 100° C. for 2 h
  5. customThe reaction was quenched with ice cold H2O
  6. filtrationthe resulting precipitate was filtered
  7. washwashed with ice cold H2O
  8. customdried
  9. customThe crude product was recrystallized with 10% MeOH/CHCl3

Sources & evidence

ORD record
ord-45b236c03c10498b8ae7feb68cbf3aa8
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

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