Sodium t-butoxide → HCID 178481628, compound

HRID 707402Notes

Reaction equation

HRID 707402 reaction equation
Cl[C:2]1[C:7]([N:8]([CH3:13])[C:9](=[O:12])OC)=[CH:6][C:5]([F:14])=[CH:4][N:3]=1.[C:15]([O:19][C:20](=[O:27])[NH:21][C@H:22]1[CH2:25][C@H:24]([NH2:26])[CH2:23]1)([CH3:18])([CH3:17])[CH3:16].CC(C)([O-])C.[Na+]>CC(C1C=C(C(C)C)C(C2C(P(C3CCCCC3)C3CCCCC3)=C(OC)C=CC=2OC)=C(C(C)C)C=1)C.C1C=[C-]C(CCN)=CC=1.Cl[Pd+].O1CCOCC1.O>[C:15]([O:19][C:20](=[O:27])[NH:21][C@H:22]1[CH2:25][C@H:24]([N:26]2[C:2]3=[N:3][CH:4]=[C:5]([F:14])[CH:6]=[C:7]3[N:8]([CH3:13])[C:9]2=[O:12])[CH2:23]1)([CH3:18])([CH3:16])[CH3:17]

Participants

7

Reactant 3

HCID 23676156Sodium t-butoxideHCID 86694180Methyl (2-chloro-5-fluoropyridin-3-yl)(methyl)carbamate2×HCID 178454111HCID 178454111, compound

Product 1

HCID 178481628HCID 178481628, compoundYield 47.4%

Reagents, catalysts & solvents 3

HCID 25112666BrettPhos PalladacycleCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
50 °C

Procedure

Methyl (2-chloro-5-fluoropyridin-3-yl)(methyl)carbamate (intermediate 37, 0.343 g, 1.569 mmol), tert-butyl(trans-3-aminocyclobutyl)carbamate (0.292 g, 1.569 mmol), BrettPhos Precatalyst (0.125 g, 0.157 mmol), and sodium tert-butoxide (0.377 g, 3.92 mmol) were mixed in 1,4-dioxane (2 mL) under an argon atmosphere. The reaction mixture was heated to 50° C. and stirred for 30 min. The reaction mixture was diluted with water and extracted once with EtOAc. The organic layer was separated, washed with saturated aqueous sodium chloride, dried over magnesium sulfate, filtered, and concentrated in vacuo. The resulting crude product was purified by silica gel column chromatography eluting with EtOAc in hexanes to yield tert-butyl(trans-3-(6-fluoro-1-methyl-2-oxo-1 h-imidazo[4,5-b]pyridin-3(2h)-yl)cyclobutyl)carbamate (0.250 g, 0.743 mmol, 47.4% yield) as a white solid.

Workup

  1. extractionextracted once with EtOAc
  2. customThe organic layer was separated
  3. washwashed with saturated aqueous sodium chloride
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe resulting crude product was purified by silica gel column chromatography
  8. washeluting with EtOAc in hexanes

Sources & evidence

ORD record
ord-769a8634e25348ccbbb573feaa5e26e0
Source dataset
uspto-grants-2015_11
Patent number
US09174992B2

Reaction notes

Loading…