Trifluoroacetic acid → 2-(isopropylamino)-6-(5-(5-(isopropylamino)-1,3,4-oxadiazol-2-yl)-1H-indol-3-yl)pyrimidin-4(3H)-one

HRID 634327Notes

Reaction equation

HRID 634327 reaction equation
[CH:1]([NH:4][C:5]1[O:6][C:7]([C:10]2[CH:11]=[C:12]3[C:16](=[CH:17][CH:18]=2)[NH:15][CH:14]=[C:13]3[C:19]2[CH:24]=[C:23]([O:25]CC3C=CC(OC)=CC=3)[N:22]=[C:21]([NH:35][CH:36]([CH3:38])[CH3:37])[N:20]=2)=[N:8][N:9]=1)([CH3:3])[CH3:2].C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH:36]([NH:35][C:21]1[NH:22][C:23](=[O:25])[CH:24]=[C:19]([C:13]2[C:12]3[C:16](=[CH:17][CH:18]=[C:10]([C:7]4[O:6][C:5]([NH:4][CH:1]([CH3:3])[CH3:2])=[N:9][N:8]=4)[CH:11]=3)[NH:15][CH:14]=2)[N:20]=1)([CH3:38])[CH3:37]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 68328419N-isopropyl-5-(3-(2-(isopropylamino)-6-((4-methoxybenzyl)oxy)pyrimidin-4-yl)-1H-indol-5-yl)-1,3,4-oxadiazol-2-amine

Product 1

HCID 1363484982-(isopropylamino)-6-(5-(5-(isopropylamino)-1,3,4-oxadiazol-2-yl)-1H-indol-3-yl)pyrimidin-4(3H)-oneYield 34%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a 15-mL round-bottomed flask was added N-isopropyl-5-(3-(2-(isopropylamino)-6-((4-methoxybenzyl)oxy)pyrimidin-4-yl)-1H-indol-5-yl)-1,3,4-oxadiazol-2-amine (77 mg, 0.150 mmol) and TFA (0.3 mL, 4.04 mmol) in DCM (1 mL). The reaction was stirred at RT for 15 min and then the solvent was removed. The residue was purified with preparative HPLC (10-50% MeCN in water with 0.1% TFA in each solvent) and the fractions containing the product were combined and concentrated in vacuo to remove MeCN. The resulting mixture was extracted with CHCl3/iPrOH (4:1) and the combined organic layers were dried (MgSO4), filtered and concentrated to give 2-(isopropylamino)-6-(5-(5-(isopropylamino)-1,3,4-oxadiazol-2-yl)-1H-indol-3-yl)pyrimidin-4(3H)-one (20.0 mg, 0.051 mmol, 33.9% yield) as a light yellow solid. MS (ESI, pos. ion) m/z: 394.1 (M+1); 1H NMR (400 MHz, DMSO-d6) δ ppm 11.90 (1H, br. s.), 10.14-10.38 (1H, m), 8.75 (1H, s), 8.15 (1H, s), 7.63-7.70 (1H, m), 7.48-7.62 (2H, m), 6.23-6.40 (1H, m), 6.03 (1H, s), 4.24 (1H, dq, J=13.3, 6.5 Hz), 3.75 (1H, dq, J=13.6, 6.6 Hz), 1.29 (6H, d, J=6.5 Hz), 1.24 (6H, d, J=6.7 Hz).

Workup

  1. customthe solvent was removed
  2. customThe residue was purified with preparative HPLC (10-50% MeCN in water with 0.1% TFA in each solvent) and the fractions
  3. additioncontaining the product
  4. concentrationconcentrated in vacuo
  5. customto remove MeCN
  6. extractionThe resulting mixture was extracted with CHCl3/iPrOH (4:1)
  7. dry with materialthe combined organic layers were dried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-36becbdb8f304d5e9153682910369fe5
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

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