Sodium Carbonate → (S)-2-amino-N-cyclopropyl-7'-(neopentyloxy)-5H-spiro[oxazole-4,9'-xanthene]-2'-carboxamide

HRID 335755Notes

Reaction equation

HRID 335755 reaction equation
Br[C:2]1[CH:15]=[CH:14][C:13]2[O:12][C:11]3[C:6](=[CH:7][C:8]([O:16][CH2:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[CH:9][CH:10]=3)[C@:5]3([CH2:25][O:24][C:23]([NH2:26])=[N:22]3)[C:4]=2[CH:3]=1.[C:27](=[O:30])([O-])[O-].[Na+].[Na+].[CH:33]1([NH2:36])[CH2:35][CH2:34]1.O1CCOCC1>CCOC(C)=O.O.C(O[Pd]CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C)(=O)C>[NH2:26][C:23]1[O:24][CH2:25][C@:5]2([N:22]=1)[C:4]1[CH:3]=[C:2]([C:27]([NH:36][CH:33]3[CH2:35][CH2:34]3)=[O:30])[CH:15]=[CH:14][C:13]=1[O:12][C:11]1[C:6]2=[CH:7][C:8]([O:16][CH2:17][C:18]([CH3:20])([CH3:19])[CH3:21])=[CH:9][CH:10]=1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 69828CyclopropylamineHCID 58466128(R)-2'-bromo-7'-(neopentyloxy)-5H-spiro[oxazole-4,9'-xanthen]-2-amine

Product 1

HCID 58466226(S)-2-amino-N-cyclopropyl-7'-(neopentyloxy)-5H-spiro[oxazole-4,9'-xanthene]-2'-carboxamide

Reagents, catalysts & solvents 3

HCID 178476741HCID 178476741, compoundCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
170 °C

Procedure

A 0.5-2 mL microwave vial charged with (R)-2′-bromo-7′-(neopentyloxy)-5H-spiro[oxazole-4,9′-xanthen]-2-amine (0.1000 g, 0.240 mmol), Mo(CO)6 (0.063 g, 0.240 mmol), acetoxy(2-(dio-tolylphosphino)benzyl)palladium (0.011 g, 0.012 mmol), sodium carbonate (0.025 g, 0.240 mmol), cyclopropylamine (0.025 mL, 0.359 mmol), and 1,4-dioxane (0.443 mL, 5.03 mmol) was sealed and heated to 170° C. for 30 minutes. The mixture was diluted with EtOAc and water and filtered through celite. The celite was washed with EtOAc and MeOH. The aqueous phase was extracted with EtOAc three times. The organic layer was dried over Na2SO4 and concentrated in vacuo. The crude was purified by silica gel chromatography (2-10% MeOH—CH2Cl2, then 10% MeOH—CH2Cl2). The product was purified again by reverse phase prep HPLC: 10-55% CH3CN (0.1% TFA)-water (0.1% TFA) in 26 min. The fractions were combined and neutralized with solid Na2CO3, extracted three times with DCM. The organic layer was concentrated to provide (S)-2-amino-N-cyclopropyl-7′-(neopentyloxy)-5H-spiro[oxazole-4,9′-xanthene]-2′-carboxamide.

Workup

  1. customwas sealed
  2. filtrationfiltered through celite
  3. washThe celite was washed with EtOAc and MeOH
  4. extractionThe aqueous phase was extracted with EtOAc three times
  5. dry with materialThe organic layer was dried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe crude was purified by silica gel chromatography (2-10% MeOH—CH2Cl2
  8. customThe product was purified again by reverse phase prep HPLC
  9. extractionextracted three times with DCM
  10. concentrationThe organic layer was concentrated

Sources & evidence

ORD record
ord-b9e22da6ab2941209cb5efb8e3593f58
Source dataset
uspto-grants-2014_11
Patent number
US08883782B2

Reaction notes

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