Hydrochloric Acid → HCID 90114088, compound

HRID 2275878Notes

Reaction equation

HRID 2275878 reaction equation
[F:1][C:2]1[CH:39]=[CH:38][CH:37]=[C:36]([F:40])[C:3]=1[CH2:4][O:5][C:6]1[C:7]2[N:8]([C:12]([C:16]([NH:18][CH:19]3[C:28]4[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=4)[N:22](C(OC(C)(C)C)=O)[CH2:21][CH2:20]3)=[O:17])=[C:13]([CH3:15])[N:14]=2)[CH:9]=[CH:10][CH:11]=1.Cl>C(OCC)C>[F:1][C:2]1[CH:39]=[CH:38][CH:37]=[C:36]([F:40])[C:3]=1[CH2:4][O:5][C:6]1[C:7]2[N:8]([C:12]([C:16]([NH:18][CH:19]3[C:28]4[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=4)[NH:22][CH2:21][CH2:20]3)=[O:17])=[C:13]([CH3:15])[N:14]=2)[CH:9]=[CH:10][CH:11]=1

Participants

4

Reactant 2

HCID 313Hydrochloric Acid2×HCID 90114618HCID 90114618, compound

Product 1

HCID 90114088HCID 90114088, compound

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent3×

Procedure

229 mg of rac-tert-butyl 4-[({8-[(2,6-difluorobenzyl)oxy]-2-methylimidazo[1,2-a]pyridin-3-yl}-carbonyl)amino]-3,4-dihydroquinoline-1(2H)-carboxylate (Example 105A, 0.41 mmol) were dissolved in 10 ml of diethyl ether, 2.05 ml of a 2 M solution of hydrochloric acid (4.09 mmol) were added and the mixture was stirred at RT overnight. Another 1.02 ml of a 2 M solution of hydrochloric acid in diethyl ether were then added, and the mixture was stirred at RT overnight. A little diethyl ether was added to the reaction mixture and the solid obtained was filtered off and washed with diethyl ether. The solid was dissolved in dichloromethane containing a little methanol and washed with saturated aqueous sodium bicarbonate solution. The organic phase was concentrated. The crude product was purified by preparative HPLC (RP18 column, mobile phase: methanol/water gradient with addition of 0.1% TFA). The product fractions were concentrated, taken up in dichloromethane and washed with saturated aqueous sodium bicarbonate solution. The organic phase was dried over sodium sulphate, filtered and concentrated. This gave 140 mg of the title compound (75% of theory).

Workup

  1. stirringthe mixture was stirred at RT overnight
  2. customthe solid obtained
  3. filtrationwas filtered off
  4. washwashed with diethyl ether
  5. dissolutionThe solid was dissolved in dichloromethane containing a little methanol
  6. washwashed with saturated aqueous sodium bicarbonate solution
  7. concentrationThe organic phase was concentrated
  8. customThe crude product was purified by preparative HPLC (RP18 column, mobile phase: methanol/water gradient with addition of 0.1% TFA)
  9. concentrationThe product fractions were concentrated
  10. washwashed with saturated aqueous sodium bicarbonate solution
  11. dry with materialThe organic phase was dried over sodium sulphate
  12. filtrationfiltered
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-9595866a08744233b3478ff4db4f041a
Source dataset
uspto-grants-2015_09
Patent number
US09126998B2

Reaction notes

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