Methanol → Ethyl-6-((2R,4S)-4-fluoro-2-(5-fluoro-2-(((S)-tetrahydrofuran-3-yl)oxy)phenyl) pyrrolidin-1-yl)imidazo[1,2-a]pyridine-3-carboxylate

HRID 1054463Notes

Reaction equation

HRID 1054463 reaction equation
[F:1][C@@H:2]1[CH2:6][N:5]([C:7]2[CH:8]=[CH:9][C:10]([NH2:13])=[N:11][CH:12]=2)[C@@H:4]([C:14]2[CH:19]=[C:18]([F:20])[CH:17]=[CH:16][C:15]=2[O:21][C@H:22]2[CH2:26][CH2:25][O:24][CH2:23]2)[CH2:3]1.[CH3:27]N(C(OC)OC)C.[CH2:35]([O:37][C:38](=[O:41])[CH2:39]Br)[CH3:36].CO>C1(C)C=CC=CC=1>[CH2:35]([O:37][C:38]([C:39]1[N:11]2[CH:12]=[C:7]([N:5]3[CH2:6][C@@H:2]([F:1])[CH2:3][C@@H:4]3[C:14]3[CH:19]=[C:18]([F:20])[CH:17]=[CH:16][C:15]=3[O:21][C@H:22]3[CH2:26][CH2:25][O:24][CH2:23]3)[CH:8]=[CH:9][C:10]2=[N:13][CH:27]=1)=[O:41])[CH3:36]

Participants

6

Reactant 4

HCID 887MethanolHCID 7748Ethyl bromoacetateHCID 78373Dimethylformamide dimethyl acetalHCID 1185905585-((2R,4S)-4-fluoro-2-(5-fluoro-2-(((S)-tetrahydrofuran-3-yl)oxy)phenyl)pyrrolidin-1-yl)pyridin-2-amine

Product 1

HCID 118590380Ethyl-6-((2R,4S)-4-fluoro-2-(5-fluoro-2-(((S)-tetrahydrofuran-3-yl)oxy)phenyl) pyrrolidin-1-yl)imidazo[1,2-a]pyridine-3-carboxylateYield 30%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
120 °C

Procedure

To a stirred solution of 5-((2R,4S)-4-fluoro-2-(5-fluoro-2-(((S)-tetrahydrofuran-3-yl)oxy)phenyl)pyrrolidin-1-yl)pyridin-2-amine (4.2 g, 11.63 mmol) in dry toluene (11 ml) was added DMF-DMA (2.9 g, 24.43 mmol) under N2 atm and stirred for 2 h at 120° C. during which complete consumption of starting material was observed by TLC, cooled it to 10° C. then added Ethylbromoacetate (4.27 g, 25.59 mmol) drop wise and methanol (4 ml) was added under N2 atm then stirred for 16 h at 120° C. Reaction mixture was cooled to room temperature and solvent was removed in vacuo and residue was dissolved in DCM (200 ml), washed with water and brine, dried over anhydrous Na2SO4 and concentrated under vacuum to get crude product. Crude was purified by column chromatography (eluted with 30-40% ethyl acetate/Hexane) to afford pale green solid (1.3 g, yield: 30%), MS (ESI): 458.2 (M+H)

Workup

  1. temperaturecooled it to 10° C.
  2. stirringatm then stirred for 16 h at 120° C
  3. customReaction mixture
  4. temperaturewas cooled to room temperature
  5. customsolvent was removed in vacuo and residue
  6. dissolutionwas dissolved in DCM (200 ml)
  7. washwashed with water and brine
  8. dry with materialdried over anhydrous Na2SO4
  9. concentrationconcentrated under vacuum
  10. customto get crude product
  11. customCrude was purified by column chromatography (eluted with 30-40% ethyl acetate/Hexane)

Sources & evidence

ORD record
ord-8ef43e5b46f44252a0b91294be26e79f
Source dataset
uspto-grants-2016_07
Patent number
US09394305B2

Reaction notes

Loading…