Isopropanol → 5-(3-(4-isopropoxypyrimidin-2-yl)-1H-indol-5-yl)-N-isopropyl-1,3,4-oxadiazol-2-amine

HRID 634246Notes

Reaction equation

HRID 634246 reaction equation
[CH3:1][CH:2]([OH:4])[CH3:3].Cl[C:6]1[CH:11]=[CH:10][N:9]=[C:8]([C:12]2[C:20]3[C:15](=[CH:16][CH:17]=[C:18]([C:21]4[O:25][C:24]([NH:26][CH:27]([CH3:29])[CH3:28])=[N:23][N:22]=4)[CH:19]=3)[N:14](S(C3C=CC(C)=CC=3)(=O)=O)[CH:13]=2)[N:7]=1.[H-].[Na+]>>[CH:2]([O:4][C:10]1[CH:11]=[CH:6][N:7]=[C:8]([C:12]2[C:20]3[C:15](=[CH:16][CH:17]=[C:18]([C:21]4[O:25][C:24]([NH:26][CH:27]([CH3:29])[CH3:28])=[N:23][N:22]=4)[CH:19]=3)[NH:14][CH:13]=2)[N:9]=1)([CH3:3])[CH3:1]

Participants

4

Reactant 3

HCID 3776IsopropanolHCID 24758Sodium hydrideHCID 867251125-(3-(4-chloropyrimidin-2-yl)-1-tosyl-1H-indol-5-yl)-N-isopropyl-1,3,4-oxadiazol-2-amine

Product 1

HCID 683289155-(3-(4-isopropoxypyrimidin-2-yl)-1H-indol-5-yl)-N-isopropyl-1,3,4-oxadiazol-2-amineYield 10.2%

Conditions

Temperature
100 °C

Procedure

A glass microwave reaction vessel was charged with IPA (1 mL, 13.06 mmol) and 5-(3-(4-chloropyrimidin-2-yl)-1-tosyl-1H-indol-5-yl)-N-isopropyl-1,3,4-oxadiazol-2-amine (80 mg, 0.157 mmol), followed by the addition of 60% of NaH in mineral oil (15.72 mg, 0.393 mmol, Aldrich). The reaction was stirred and heated in a Initiator microwave reactor at 100° C. for 30 min, then the solvent was removed. 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 5-(3-(4-isopropoxypyrimidin-2-yl)-1H-indol-5-yl)-N-isopropyl-1,3,4-oxadiazol-2-amine (6.0 mg, 0.016 mmol, 10.09%) as an off-white solid. MS (ESI, pos. ion) m/z: 379.1 (M+1); 1H NMR (400 MHz, DMSO-d6) δ ppm 11.99 (1H, br. s.), 9.00 (1H, s), 8.50 (1H, d, J=5.7 Hz), 8.30 (1H, s), 7.52-7.72 (3H, m), 6.60 (1H, d, J=5.9 Hz), 5.47-5.62 (1H, m), 3.67-3.81 (1H, m), 1.42 (6H, d, J=6.1 Hz), 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-188c49fef8e0459f8d83f99d5f7c02d4
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

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