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

HRID 634327노트

반응식

HRID 634327 반응식
[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]

참가 물질

4

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-36becbdb8f304d5e9153682910369fe5
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09321756B2

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