1-Methylpiperazine → n-(3-(4-(1h-Indazol-5-ylamino)-7-methoxy-6-(2-(4-methylpiperazin-1-yl)ethoxy)-quinazolin-2-yl)phenyl) butyramide di-hydrochloride salt

HRID 1808544Notes

Reaction equation

HRID 1808544 reaction equation
[C:1]([NH:6][C:7]1[CH:8]=[C:9]([C:13]2[N:22]=[C:21]([NH:23][C:24]3[CH:25]=[C:26]4[C:30](=[CH:31][CH:32]=3)[N:29](C(OC(C)(C)C)=O)[N:28]=[CH:27]4)[C:20]3[C:15](=[CH:16][C:17]([O:44][CH3:45])=[C:18]([O:40][CH2:41][CH2:42][Cl:43])[CH:19]=3)[N:14]=2)[CH:10]=[CH:11][CH:12]=1)(=[O:5])[CH2:2][CH2:3][CH3:4].[CH3:46][N:47]1[CH2:52][CH2:51][NH:50][CH2:49][CH2:48]1>CS(C)=O>[ClH:43].[ClH:43].[NH:29]1[C:30]2[C:26](=[CH:25][C:24]([NH:23][C:21]3[C:20]4[C:15](=[CH:16][C:17]([O:44][CH3:45])=[C:18]([O:40][CH2:41][CH2:42][N:50]5[CH2:51][CH2:52][N:47]([CH3:46])[CH2:48][CH2:49]5)[CH:19]=4)[N:14]=[C:13]([C:9]4[CH:8]=[C:7]([NH:6][C:1](=[O:5])[CH2:2][CH2:3][CH3:4])[CH:12]=[CH:11][CH:10]=4)[N:22]=3)=[CH:32][CH:31]=2)[CH:27]=[N:28]1

Participants

4

Reactant 2

HCID 531671-MethylpiperazineHCID 59361971tert-butyl 5-(2-(3-butyramidophenyl)-6-(2-chloroethoxy)-7-methoxyquinazolin-4-ylamino)-1H-indazole-1-carboxylate

Product 1

HCID 66826237n-(3-(4-(1h-Indazol-5-ylamino)-7-methoxy-6-(2-(4-methylpiperazin-1-yl)ethoxy)-quinazolin-2-yl)phenyl) butyramide di-hydrochloride saltYield 43%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
85 °C

Procedure

To a solution of tert-butyl 5-(2-(3-butyramidophenyl)-6-(2-chloroethoxy)-7-methoxyquinazolin-4-ylamino)-1H-indazole-1-carboxylate (0.170 g, 0.299 mmol) in DMSO (2 mL) was added 1-methylpiperazine (0.5 mL). The subsequent mixture was heated at 85° C. for 2.5 h upon which it was allowed to cool to RT and poured into ice-water (100 mL). A precipitate formed which was collected via filtration and it was dried under vacuum. The precipitate was purified via 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 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)-7-methoxy-6-(2-(4-methylpiperazin-1-yl)ethoxy)-quinazolin-2-yl)phenyl)butyramide di-hydrochloride salt (0.085 g, 0.128 mmol, 43% over two steps). MS 595 (M+1). HPLC retention time 4.337 mins.

Workup

  1. temperatureto cool to RT
  2. customA precipitate formed which
  3. filtrationwas collected via filtration and it
  4. customwas dried under vacuum
  5. customThe precipitate was purified via preparative TLC (SiO2, CH2Cl2:MeOH:NH4OH 9:1:0.1)
  6. customThe volatiles were removed in vacuo
  7. customthe residue was triturated with Et2O
  8. filtrationfiltered
  9. customdried under vacuum

Sources & evidence

ORD record
ord-f8d0aa7a90fc447993a843aba1733e71
Source dataset
uspto-grants-2013_01
Patent number
US08357693B2

Reaction notes

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