Potassium Hydroxide → (1S,3R)-3-(5'-chloro-6-(3-fluorobenzylamino)-2,4'-bipyridin-2'-yl-amino)cyclopentanecarboxylic acid

HRID 1963932Notes

Reaction equation

HRID 1963932 reaction equation
[Cl:1][C:2]1[C:3]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([NH:15][CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=3)[N:10]=2)=[CH:4][C:5](F)=[N:6][CH:7]=1.[NH2:24][C@@H:25]1[CH2:29][CH2:28][C@H:27]([C:30]([OH:32])=[O:31])[CH2:26]1.[OH-].[K+]>O1CCOCC1>[Cl:1][C:2]1[C:3]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([NH:15][CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=3)[N:10]=2)=[CH:4][C:5]([NH:24][C@@H:25]2[CH2:29][CH2:28][C@H:27]([C:30]([OH:32])=[O:31])[CH2:26]2)=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 14797Potassium HydroxideHCID 15020343-Aminocyclopentane-1-carboxylic acidHCID 58127193HCID 58127193, compound

Product 1

HCID 66936933(1S,3R)-3-(5'-chloro-6-(3-fluorobenzylamino)-2,4'-bipyridin-2'-yl-amino)cyclopentanecarboxylic acidYield 7.5%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To 5′-chloro-2′-fluoro-N-(3-fluorobenzyl)-2,4′-bipyridin-6-amine (100 mg, 0.301 mmol), was added (1S,3R)-3-aminocyclopentanecarboxylic acid (117 mg, 0.904 mmol), powdered potassium hydroxide (85 mg, 1.507 mmol) and dioxane (1 ml). The reaction mixture was stirred at 100° C. for 18 hr in a sealed vessel and followed by LCMS. The crude reaction mixture was partitioned between 30 mL saturated ammonium chloride and 30 mL ethyl acetate. The organic layer was removed, dried over sodium sulfate, and reduced. This was redissolved in 1.5 mL DMSO, filtered, and purified through prep LC. The product fractions were combined and extracted with 50 mL ethyl acetate, which was dried over sodium sulfate, and concentrated to constant mass. 10 mg of the desired compound was obtained. LCMS (m/z): 441.2 (MH+), retention time=0.68 min. 1H NMR (400 MHz, CHLOROFORM-d, 25° C.) δ ppm 1.59 (m, 2 H) 1.83 (m, 2 H) 1.99 (m, 1 H) 2.72 (m, 1 H) 3.40 (br. s., 1 H) 3.78 (br. s., 1 H) 4.42 (br. s., 1 H) 5.48 (br. s., 1 H) 6.29 (d, J=8.22 Hz, 1 H) 6.50 (s, 1 H) 6.80-6.92 (m, 2 H) 6.95-7.10 (m, 2 H) 7.16-7.25 (m, 1 H) 7.38 (t, J=8.02 Hz, 1 H) 7.89 (s, 1 H).

Workup

  1. customThe crude reaction mixture
  2. customwas partitioned between 30 mL saturated ammonium chloride and 30 mL ethyl acetate
  3. customThe organic layer was removed
  4. dry with materialdried over sodium sulfate
  5. dissolutionThis was redissolved in 1.5 mL DMSO
  6. filtrationfiltered
  7. custompurified through prep LC
  8. extractionextracted with 50 mL ethyl acetate, which
  9. dry with materialwas dried over sodium sulfate
  10. concentrationconcentrated to constant mass

Sources & evidence

ORD record
ord-664e27df708347c48642e95571410d12
Source dataset
uspto-grants-2013_04
Patent number
US08415381B2

Reaction notes

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