Hydrochloric Acid → HCID 90114000, compound

HRID 2275877Notes

Reaction equation

HRID 2275877 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([O:31][CH2:32][C:33]2[C:38]([F:39])=[CH:37][CH:36]=[CH:35][C:34]=2[F:40])[C:5]2[N:6]([C:8]([C:12]([NH:14][CH:15]3[C:23]4[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=4)[N:17](C(OC(C)(C)C)=O)[CH2:16]3)=[O:13])=[C:9]([CH3:11])[N:10]=2)[CH:7]=1.Cl>C(OCC)C>[Cl:1][C:2]1[CH:3]=[C:4]([O:31][CH2:32][C:33]2[C:34]([F:40])=[CH:35][CH:36]=[CH:37][C:38]=2[F:39])[C:5]2[N:6]([C:8]([C:12]([NH:14][CH:15]3[C:23]4[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=4)[NH:17][CH2:16]3)=[O:13])=[C:9]([CH3:11])[N:10]=2)[CH:7]=1

Participants

4

Reactant 2

HCID 313Hydrochloric Acid4×HCID 90114219HCID 90114219, compound

Product 1

HCID 90114000HCID 90114000, compound

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent6×

Procedure

141 mg of rac-tert-butyl 3-[({6-chloro-8-[(2,6-difluorobenzyl)oxy]-2-methylimidazo[1,2-a]pyridin-3-yl}carbonyl)amino]indolin-1-carboxylate (Example 104A, 0.25 mmol) were dissolved in 1.2 ml of diethyl ether, 1.24 ml of a 2 M solution of hydrochloric acid in diethyl ether (2.48 mmol) were added and the mixture was stirred at RT overnight. 1.24 ml of a 2 M solution of hydrochloric acid in diethyl ether (2.48 mmol) were then added, and the mixture was stirred at RT for 3 d. 1.24 ml of a 2 M solution of hydrochloric acid in diethyl ether (2.48 mmol) were then added a little at a time and the mixture was stirred under reflux for 4 h (with additional diethyl ether and hydrochloric acid in diethyl ether being added a little at a time!). The precipitate was filtered off and washed thoroughly with diethyl ether, and ethyl acetate and saturated aqueous sodium bicarbonate solution were then added. After phase separation, the aqueous phase was extracted twice with ethyl acetate. The combined organic phases were dried over sodium sulphate and filtered, and the filtrate was concentrated and lyophilized. This gave 93 mg of the title compound (80% of theory).

Workup

  1. stirringthe mixture was stirred at RT for 3 d
  2. stirringthe mixture was stirred
  3. additionadded a little at a time
  4. filtrationThe precipitate was filtered off
  5. washwashed thoroughly with diethyl ether, and ethyl acetate and saturated aqueous sodium bicarbonate solution
  6. additionwere then added
  7. customAfter phase separation
  8. extractionthe aqueous phase was extracted twice with ethyl acetate
  9. dry with materialThe combined organic phases were dried over sodium sulphate
  10. filtrationfiltered
  11. concentrationthe filtrate was concentrated

Sources & evidence

ORD record
ord-aef36bd271274aa3883c552221093579
Source dataset
uspto-grants-2015_09
Patent number
US09126998B2

Reaction notes

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