Potassium Carbonate → (S)-3-bromo-7-(2-fluoropyridin-3-yl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-thiazol]-2'-amine

HRID 335993Notes

Reaction equation

HRID 335993 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C@:15]3([CH2:19][S:18][C:17]([NH2:20])=[N:16]3)[C:14]3[C:9](=[CH:10][CH:11]=[C:12](I)[CH:13]=3)[O:8][C:5]2=[N:6][CH:7]=1.C(=O)([O-])[O-].[K+].[K+].[F:28][C:29]1[C:34](B(O)O)=[CH:33][CH:32]=[CH:31][N:30]=1.O1CCOCC1>O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CO.CCOC(C)=O>[Br:1][C:2]1[CH:3]=[C:4]2[C@:15]3([CH2:19][S:18][C:17]([NH2:20])=[N:16]3)[C:14]3[C:9](=[CH:10][CH:11]=[C:12]([C:34]4[C:29]([F:28])=[N:30][CH:31]=[CH:32][CH:33]=4)[CH:13]=3)[O:8][C:5]2=[N:6][CH:7]=1

Participants

9

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 27832702-Fluoropyridine-3-boronic acidHCID 58466127(S)-3-Bromo-7-iodo-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-thiazol]-2'-amine

Product 1

HCID 67438436(S)-3-bromo-7-(2-fluoropyridin-3-yl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-thiazol]-2'-amineYield 46.1%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolventHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A pressure reaction vessel was charged with (S)-3-bromo-7-iodo-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-thiazol]-2′-amine (1.51 g, 3.19 mmol), potassium carbonate (2.20 g, 15.95 mmol), 2-fluoropyridin-3-ylboronic acid (0.72 g, 5.10 mmol), tetrakis(triphenylphosphine)palladium(0) (0.37 g, 0.32 mmol), dioxane (21.3 mL) and water (10.6 mL). The reaction was stirred and heated at 100° C. for 1 h. After cooling to rt, the reaction was diluted with water (25 mL) and poured into a separatory funnel containing EtOAc (50 mL). The layers were separated and the aqueous layer was extracted with EtOAc (1×100 mL). The combined organic layers were washed with water, dried over sodium sulfate, filtered, and concentrated in vacuo to provide a brown foam that was purified by silica gel chromatography (Redi-Sep pre-packed silica gel column (40 g), 0-100% EtOAc in 90:10 CH2Cl2:CH3OH to provide a white solid, (S)-3-bromo-7-(2-fluoropyridin-3-yl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-thiazol]-2′-amine (0.65 g, 1.47 mmol). MS m/z=443.0 [M+H]+. Calc'd for C19H12BrFN4OS: 441.99.

Workup

  1. customA pressure reaction vessel
  2. temperatureAfter cooling to rt
  3. additionpoured into a separatory funnel
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted with EtOAc (1×100 mL)
  6. washThe combined organic layers were washed with water
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto provide a brown foam that
  11. customwas purified by silica gel chromatography (Redi-Sep pre-packed silica gel column (40 g), 0-100% EtOAc in 90:10 CH2Cl2

Sources & evidence

ORD record
ord-7216430d53c34fc19a4d1b09134f8f18
Source dataset
uspto-grants-2014_11
Patent number
US08883782B2

Reaction notes

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