Sodium Methoxide → N-isopropyl-5-(3-(4-methoxypyrimidin-2-yl)-1H-indol-5-yl)-1,3,4-oxadiazol-2-amine

HRID 634245Notes

Reaction equation

HRID 634245 reaction equation
Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([C:17]4[O:21][C:20]([NH:22][CH:23]([CH3:25])[CH3:24])=[N:19][N:18]=4)[CH:15]=3)[N:10](S(C3C=CC(C)=CC=3)(=O)=O)[CH:9]=2)[N:3]=1.[CH3:36][O-:37].[Na+]>CO>[CH:23]([NH:22][C:20]1[O:21][C:17]([C:14]2[CH:15]=[C:16]3[C:11](=[CH:12][CH:13]=2)[NH:10][CH:9]=[C:8]3[C:4]2[N:3]=[C:2]([O:37][CH3:36])[CH:7]=[CH:6][N:5]=2)=[N:18][N:19]=1)([CH3:24])[CH3:25]

Participants

4

Reactant 2

HCID 10942334Sodium MethoxideHCID 867251125-(3-(4-chloropyrimidin-2-yl)-1-tosyl-1H-indol-5-yl)-N-isopropyl-1,3,4-oxadiazol-2-amine

Product 1

HCID 68328355N-isopropyl-5-(3-(4-methoxypyrimidin-2-yl)-1H-indol-5-yl)-1,3,4-oxadiazol-2-amineYield 61.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
100 °C

Procedure

A glass microwave reaction vessel was charged with 5-(3-(4-chloropyrimidin-2-yl)-1-tosyl-1H-indol-5-yl)-N-isopropyl-1,3,4-oxadiazol-2-amine (50 mg, 0.098 mmol) and sodium methoxide (18.57 mg, 0.344 mmol, Alfa Aesar) in MeOH (1 mL). The reaction was stirred and heated in a Initiator microwave reactor at 85° C. for 30 min and 100° C. for 1 h. The solvent was removed and the residue was purified with RP-HPLC (eluent: 10-50% MeCN in water with 0.1% TFA). The fractions containing the product were combined and concentrated to remove AcCN. The remaining mixture was neutralized with NH4OH and filtered and dried to give N-isopropyl-5-(3-(4-methoxypyrimidin-2-yl)-1H-indol-5-yl)-1,3,4-oxadiazol-2-amine (21.0 mg, 0.060 mmol, 61.0%) as an off-white solid. MS (ESI, pos. ion) m/z: 351.0 (M+1). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.98 (1H, br. s.), 9.04 (1H, s), 8.52 (1H, d, J=5.7 Hz), 8.32 (1H, s), 7.69 (1H, d, J=8.6 Hz), 7.58 (2H, dd, J=13.4, 7.9 Hz), 6.68 (1H, d, J=5.7 Hz), 4.09 (3H, s), 3.66-3.82 (1H, m), 1.23 (6H, d, J=6.5 Hz)

Workup

  1. customA glass microwave reaction vessel
  2. customThe solvent was removed
  3. customthe residue was purified with RP-HPLC (eluent: 10-50% MeCN in water with 0.1% TFA)
  4. additionThe fractions containing the product
  5. concentrationconcentrated
  6. customto remove AcCN
  7. filtrationfiltered
  8. customdried

Sources & evidence

ORD record
ord-bf5a39e0dc9a40b2b11ca56b309631b0
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

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