n-(3-(4-(1h-Indazol-5-ylamino)-6-(2-(4-methylpiperazin-1-yl)ethoxy)quinazolin-2-yl)phenyl)butyramide di-hydrochloride salt → N-(3-(4-(1H-indazol-5-ylamino)-6-(2-(4-methylpiperazin-1-yl)ethoxy)-quinazolin-2-yl)phenyl)butyramide

HRID 61680Notes

Reaction equation

HRID 61680 reaction equation
Cl.Cl.[NH:3]1[C:11]2[C:6](=[CH:7][C:8]([NH:12][C:13]3[C:22]4[C:17](=[CH:18][CH:19]=[C:20]([O:23][CH2:24][CH2:25][N:26]5[CH2:31][CH2:30][N:29]([CH3:32])[CH2:28][CH2:27]5)[CH:21]=4)[N:16]=[C:15]([C:33]4[CH:34]=[C:35]([NH:39][C:40](=[O:44])[CH2:41][CH2:42][CH3:43])[CH:36]=[CH:37][CH:38]=4)[N:14]=3)=[CH:9][CH:10]=2)[CH:5]=[N:4]1>C(Cl)Cl>[NH:3]1[C:11]2[C:6](=[CH:7][C:8]([NH:12][C:13]3[C:22]4[C:17](=[CH:18][CH:19]=[C:20]([O:23][CH2:24][CH2:25][N:26]5[CH2:27][CH2:28][N:29]([CH3:32])[CH2:30][CH2:31]5)[CH:21]=4)[N:16]=[C:15]([C:33]4[CH:34]=[C:35]([NH:39][C:40](=[O:44])[CH2:41][CH2:42][CH3:43])[CH:36]=[CH:37][CH:38]=4)[N:14]=3)=[CH:9][CH:10]=2)[CH:5]=[N:4]1

Participants

3

Reactant 1

HCID 66826907n-(3-(4-(1h-Indazol-5-ylamino)-6-(2-(4-methylpiperazin-1-yl)ethoxy)quinazolin-2-yl)phenyl)butyramide di-hydrochloride salt

Product 1

HCID 25012252N-(3-(4-(1H-indazol-5-ylamino)-6-(2-(4-methylpiperazin-1-yl)ethoxy)-quinazolin-2-yl)phenyl)butyramide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The combined compounds were taken up in CH2Cl2 (2 mL) TFA (4 mL) was added. The resulting mixture was stirred at RT for 4 h, upon which the volatiles were removed in vacuo. The residue was neutralized with sat. NaHCO3 and extracted with THF (3×25 mL). The combined organics were washed with brine (1×20 mL), dried (Na2SO4) and purified by preparative TLC (SiO2, CH2Cl2:MeOH:NH4OH 9:1:0.1). The purified compound was taken up in CH2Cl2 (2 mL) and HCl (4M in 1,4 dioxane, 10 mL) and was stirred at RT for 4 h. The volatiles were removed in vacuo and the residue was triturated with Et2O, filtered and dried under vacuum to give N-(3-(4-(1H-indazol-5-ylamino)-6-(2-(4-methylpiperazin-1-yl)ethoxy)quinazolin-2-yl)phenyl)butyramide di-hydrochloride salt (0.067 g, 0.105 mmol, 42% over two steps). MS 565 (M+1). HPLC retention time 4.30 mins.

Workup

  1. additionwas added
  2. customwere removed in vacuo
  3. extractionextracted with THF (3×25 mL)
  4. washThe combined organics were washed with brine (1×20 mL)
  5. dry with materialdried (Na2SO4)
  6. custompurified by preparative TLC (SiO2, CH2Cl2:MeOH:NH4OH 9:1:0.1)
  7. stirringHCl (4M in 1,4 dioxane, 10 mL) and was stirred at RT for 4 h
  8. customThe volatiles were removed in vacuo
  9. customthe residue was triturated with Et2O
  10. filtrationfiltered
  11. customdried under vacuum

Sources & evidence

ORD record
ord-7e65fcac86624163ad4a56a3fa56280e
Source dataset
uspto-grants-2016_09
Patent number
US09440961B2

Reaction notes

Loading…