Cesium carbonate → (5)-7-(2-Fluoropyridin-3-yl)-3-(neopentyloxy)-5',6'-dihydrospiro[chromeno[2,3-b]pyridine-5,4'-[1,3]oxazin]-2'-amine

HRID 455706Notes

Reaction equation

HRID 455706 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].I[CH2:8][C:9]([CH3:12])([CH3:11])[CH3:10].[F:13][C:14]1[C:19]([C:20]2[CH:21]=[C:22]3[C@@:33]4([CH2:38][CH2:37][O:36][C:35](/[N:39]=C/N(C)C)=[N:34]4)[C:32]4[C:27](=[N:28][CH:29]=[C:30]([OH:44])[CH:31]=4)[O:26][C:23]3=[CH:24][CH:25]=2)=[CH:18][CH:17]=[CH:16][N:15]=1>CN(C=O)C>[F:13][C:14]1[C:19]([C:20]2[CH:21]=[C:22]3[C@@:33]4([CH2:38][CH2:37][O:36][C:35]([NH2:39])=[N:34]4)[C:32]4[C:27](=[N:28][CH:29]=[C:30]([O:44][CH2:8][C:9]([CH3:12])([CH3:11])[CH3:10])[CH:31]=4)[O:26][C:23]3=[CH:24][CH:25]=2)=[CH:18][CH:17]=[CH:16][N:15]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 84953Propane, 1-iodo-2,2-dimethyl-HCID 87401119N'-[(4S)-7'-(2-fluoro-3-pyridinyl)-3'-hydroxyspiro[5,6-dihydro-1,3-oxazine-4,5'-chromeno[2,3-b]pyridine]-2-yl]-N,N-dimethylmethanimidamide

Product 1

HCID 58465919(5)-7-(2-Fluoropyridin-3-yl)-3-(neopentyloxy)-5',6'-dihydrospiro[chromeno[2,3-b]pyridine-5,4'-[1,3]oxazin]-2'-amineYield 1.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

In a 35-mL resealable vessel, cesium carbonate (0.621 g, 1.905 mmol), 1-iodo-2,2-dimethylpropane (0.211 mL, 1.587 mmol), and crude (S,E)-N′-(7-(2-fluoropyridin-3-yl)-3-hydroxy-5′,6′-dihydrospiro[chromeno[2,3-b]pyridine-5,4′-[1,3]oxazin]-2′-yl)-N,N-dimethylformimidamide (0.344 g, 0.794 mmol) were taken up in DMF (8 mL). The vessel was sealed and heated in a 100° C. oil bath. After 6 h, the reaction was concentrated. The residue was taken up in 10% MeOH/DCM (120 mL) and the organic layer was extracted with water (2×10 mL). The organic layer was dried over MgSO4, filtered and concentrated. The residue was taken up in dioxane (8 mL), and a dioxane solution of HCl (4 M, 2 mL) was added. The vessel was sealed and heated in a 60° C. oil bath. After 1 h, the reaction was concentrated. The residue was diluted with water (30 mL) and the aqueous phase was extracted with 10% MeOH/DCM (3×50 mL). The organics were dried over magnesium sulfate, filtered, and concentrated. The material was purified by chromatography using 65:35:0.5:1 EtOAc-hexane-MeOH-Et3N to afford (S)-7-(2-fluoropyridin-3-yl)-3-(neopentyloxy)-5′,6′-dihydrospiro[chromeno[2,3-b]pyridine-5,4′-[1,3]oxazin]-2′-amine (4.5 mg, 0.010 mmol). MS (m/z) 449 (M+H)+.

Workup

  1. customThe vessel was sealed
  2. concentrationthe reaction was concentrated
  3. extractionthe organic layer was extracted with water (2×10 mL)
  4. dry with materialThe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. additiona dioxane solution of HCl (4 M, 2 mL) was added
  8. customThe vessel was sealed
  9. temperatureheated in a 60° C. oil bath
  10. waitAfter 1 h
  11. concentrationthe reaction was concentrated
  12. additionThe residue was diluted with water (30 mL)
  13. extractionthe aqueous phase was extracted with 10% MeOH/DCM (3×50 mL)
  14. dry with materialThe organics were dried over magnesium sulfate
  15. filtrationfiltered
  16. concentrationconcentrated
  17. customThe material was purified by chromatography

Sources & evidence

ORD record
ord-c190a82c0f004e3180fbe57c47fb26a2
Source dataset
uspto-grants-2013_07
Patent number
US08497264B2

Reaction notes

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