Chloroacetyl chloride → tert-butyl 5-(2-(3-(2-chloroacetamido)phenyl)quinazolin-4-ylamino)-1H-indazole-1-carboxylate

HRID 1808413Notes

Reaction equation

HRID 1808413 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[N:17]=[C:16]([NH:18][C:19]3[CH:20]=[C:21]4[C:25](=[CH:26][CH:27]=3)[N:24]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[N:23]=[CH:22]4)[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[N:9]=2)[CH:5]=[CH:6][CH:7]=1.C1COCC1.C([O-])(O)=O.[Na+].[Cl:45][CH2:46][C:47](Cl)=[O:48]>CCOC(C)=O>[Cl:45][CH2:46][C:47]([NH:1][C:2]1[CH:3]=[C:4]([C:8]2[N:17]=[C:16]([NH:18][C:19]3[CH:20]=[C:21]4[C:25](=[CH:26][CH:27]=3)[N:24]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[N:23]=[CH:22]4)[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[N:9]=2)[CH:5]=[CH:6][CH:7]=1)=[O:48]

Participants

6

Reactant 4

HCID 6577Chloroacetyl chloride2×HCID 8028TetrahydrofuranHCID 516892Sodium BicarbonateHCID 66825994tert-butyl 5-(2-(3-aminophenyl)quinazolin-4-ylamino)-1H-indazole-1-carboxylate

Product 1

HCID 56949464tert-butyl 5-(2-(3-(2-chloroacetamido)phenyl)quinazolin-4-ylamino)-1H-indazole-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of tert-butyl 5-(2-(3-aminophenyl)quinazolin-4-ylamino)-1H-indazole-1-carboxylate (1.0 g, 2.21 mmol) in EtOAc:THF:sat'd NaHCO3 (110 mL: 30 mL: 50 mL) was added 2-chloroacetyl chloride (1 mL, 12.6 mmol) and stirred at RT for 2.5 hr. The reaction mixture was stirred at RT for 1.5 h. Another addition of 2-chloroacetyl chloride (0.5 mL) was added and continued to stir for 2 h. Concentrated in vacuo to remove volatiles and residue was washed with 5% citric acid (2×50 mL), water (2×100 mL), and sat'd NaCl (1×50 mL). The organic layer was dried under Na2SO4 and concentrated in vacuo to give the desired product tert-butyl 5-(2-(3-(2-chloroacetamido)phenyl)quinazolin-4-ylamino)-1H-indazole-1-carboxylate. (1.02 g, 87%)

Workup

  1. stirringThe reaction mixture was stirred at RT for 1.5 h
  2. additionwas added
  3. stirringto stir for 2 h
  4. concentrationConcentrated in vacuo
  5. customto remove volatiles and residue
  6. washwas washed with 5% citric acid (2×50 mL), water (2×100 mL), and sat'd NaCl (1×50 mL)
  7. customThe organic layer was dried under Na2SO4
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-67b5627545aa4a4985f5b031378a7688
Source dataset
uspto-grants-2013_01
Patent number
US08357693B2

Reaction notes

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