Hydrochloric Acid → 8-((cis)-4-Fluoropyrrolidin-3-yloxy)-2-(7-(2-methoxyethoxy)imidazo[1,2-a]pyridin-3-yl)quinoline hydrochloride salt

HRID 1095681Notes

Reaction equation

HRID 1095681 reaction equation
[F:1][C@H:2]1[C@@H:6]([O:7][C:8]2[CH:9]=[CH:10][CH:11]=[C:12]3[C:17]=2[N:16]=[C:15]([C:18]2[N:22]4[CH:23]=[CH:24][C:25]([O:27][CH2:28][CH2:29][O:30][CH3:31])=[CH:26][C:21]4=[N:20][CH:19]=2)[CH:14]=[CH:13]3)[CH2:5][N:4](C(OCC2C=CC=CC=2)=O)[CH2:3]1.[ClH:42]>[Pd].C(O)C>[ClH:42].[F:1][C@H:2]1[CH2:3][NH:4][CH2:5][C@H:6]1[O:7][C:8]1[CH:9]=[CH:10][CH:11]=[C:12]2[C:17]=1[N:16]=[C:15]([C:18]1[N:22]3[CH:23]=[CH:24][C:25]([O:27][CH2:28][CH2:29][O:30][CH3:31])=[CH:26][C:21]3=[N:20][CH:19]=1)[CH:14]=[CH:13]2

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 131729509(cis)-Benzyl 3-fluoro-4-(2-(7-(2-methoxyethoxy)imidazo[1,2-a]pyridin-3-yl)quinolin-8-yloxy)pyrrolidine-1-carboxylate

Product 1

HCID 667814168-((cis)-4-Fluoropyrrolidin-3-yloxy)-2-(7-(2-methoxyethoxy)imidazo[1,2-a]pyridin-3-yl)quinoline hydrochloride salt

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

Crude (cis)-benzyl 3-fluoro-4-(2-(7-(2-methoxyethoxy)imidazo[1,2-a]pyridin-3-yl)quinolin-8-yloxy)pyrrolidine-1-carboxylate (1.0 g, 2.0 mmol) and palladium on carbon (1 g, 50% on a molar basis) were added to a mixture of ethanol and 1% HCl (v/v) and placed under hydrogen in a balloon with vigorous stirring. After 18 hours, the crude mixture was passed through Celite, rinsed several times with ethanol, and the collected filtrate was evaporated. The crude material was purified on silica gel using a 6% solution of ammonium hydroxide in methanol and dichloromethane to yield free base product, which, when subjected to HCl in dichloromethane and subsequent precipitation in diethyl ether yielded 150 mg (16% isolated yield) of highly pure product. MS APCI (+) m/z 423.3 (M+1) detected.

Workup

  1. washrinsed several times with ethanol
  2. customthe collected filtrate was evaporated
  3. customThe crude material was purified on silica gel using a 6% solution of ammonium hydroxide in methanol and dichloromethane
  4. customto yield free base product, which, when
  5. customsubjected to HCl in dichloromethane and subsequent precipitation in diethyl ether
  6. customyielded
  7. custom150 mg (16% isolated yield) of highly pure product

Sources & evidence

ORD record
ord-655fddde1ca244da82db9adcf297bbe1
Source dataset
uspto-grants-2012_03
Patent number
US08138181B2

Reaction notes

Loading…