Hydrochloric Acid → 2-(6-(1H-Indol-4-yl)-1H-indazol-4-yl)-5-((4-isopropylpiperazin-1-yl)methyl)oxazole hydrochloride

HRID 520647Notes

Reaction equation

HRID 520647 reaction equation
[NH:1]1[C:9]2[C:4](=[C:5]([C:10]3[CH:18]=[C:17]4[C:13]([CH:14]=[N:15][NH:16]4)=[C:12]([C:19]4[O:20][C:21]([CH2:24][N:25]5[CH2:30][CH2:29][N:28]([CH:31]([CH3:33])[CH3:32])[CH2:27][CH2:26]5)=[CH:22][N:23]=4)[CH:11]=3)[CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.[ClH:34].C(OCC)C>O1CCCC1>[ClH:34].[NH:1]1[C:9]2[C:4](=[C:5]([C:10]3[CH:18]=[C:17]4[C:13]([CH:14]=[N:15][NH:16]4)=[C:12]([C:19]4[O:20][C:21]([CH2:24][N:25]5[CH2:26][CH2:27][N:28]([CH:31]([CH3:33])[CH3:32])[CH2:29][CH2:30]5)=[CH:22][N:23]=4)[CH:11]=3)[CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 49784002Nemiralisib

Product 1

HCID 497840842-(6-(1H-Indol-4-yl)-1H-indazol-4-yl)-5-((4-isopropylpiperazin-1-yl)methyl)oxazole hydrochloride

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
60 °C

Procedure

A solution of 6-(1H-indol-4-yl)-4-(5-{[4-(1-methylethyl)-1-piperazinyl]methyl}-1,3-oxazol-2-yl)-1H-indazole in tetrahydrofuran (THF) (7.5 mL) was heated to 60° C. under nitrogen. 2M hydrochloric acid in diethyl ether (0.567 mL, 1.135 mmol) and tetrahydrofuran (THF) (0.5 mL) were mixed and added via a dropping funnel. The solution was stirred at 60° C. for 30 mins before being slowly cooled to RT. After stirring at RT for a further 30 mins the solid was filtered off, then recombined with the liquors and evaporated to dryness. THF (10 mL) was added and the slurry was cycled from RT to reflux 3 times (30 mins hold at higher/low temp). The slurry was stirred at RT for one hour then filtered under vacuum and the resultant solid dried in a vacuum oven at 50° C. overnight to give the title compound as a an off-white solid (322 mg).

Workup

  1. additionadded via a dropping funnel
  2. temperaturebefore being slowly cooled to RT
  3. stirringAfter stirring at RT for a further 30 mins the solid
  4. filtrationwas filtered off
  5. customevaporated to dryness
  6. additionTHF (10 mL) was added
  7. customwas cycled from RT
  8. temperatureto reflux 3 times (30 mins hold at higher/low temp)
  9. stirringThe slurry was stirred at RT for one hour
  10. filtrationthen filtered under vacuum
  11. customthe resultant solid dried in a vacuum oven at 50° C. overnight

Sources & evidence

ORD record
ord-1371d37beee74a72be04262dffc62254
Source dataset
uspto-grants-2016_05
Patent number
US09326987B2

Reaction notes

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