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

HRID 335989
Notes
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Reaction equation

HRID 335989 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[CH:34]=[CH:33][N:32]=[CH:31][C:30]=1B(O)O.O1CCOCC1>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.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:30]4[CH:31]=[N:32][CH:33]=[CH:34][C:29]=4[F:28])[CH:13]=3)[O:8][C:5]2=[N:6][CH:7]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 27827734-Fluoropyridine 3-boronic acid2×HCID 58466127(S)-3-Bromo-7-iodo-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-thiazol]-2'-amine

Product 1

HCID 67438006(S)-3-bromo-7-(4-fluoropyridin-3-yl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-thiazol]-2'-amineYield 46%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalyst2×HCID 962WaterSolvent

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 (1.2 g, 2.53 mmol, prepared as described in Method BB26), potassium carbonate (1.75 g, 12.66 mmol), 4-fluoropyridin-3-ylboronic acid (0.71 g, 5.06 mmol), tetrakis(triphenylphosphine)palladium(0) (0.29 g, 0.25 mmol), dioxane (16.87 mL) and water (8.44 mL). The reaction was stirred and heated at 100° C. for 45 min. After cooling for rt, LCMS showed about 50% conversion. More Pd(PPh3)4 (30 mg) and 4-fluoropyridin-3-ylboronic acid (300 mg) were added and reaction was heated at 100° C. for another 30 min. After cooling for rt, the organic layer was separated with a separatory funnel, dried over sodium sulfate, filtered, and concentrated to afford yellow oil which was purified with reverse phase HPLC. Fractions containing product were concentrated and saturated aq. NaHCO3 (25 mL) was added. A white solid precipitated out of solution which was filtered off and dried to afford a white solid, (S)-3-bromo-7-(4-fluoropyridin-3-yl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-thiazol]-2′-amine (0.51 g, 1.15 mmol, 46% yield). MS m/z=443.0 [M+H]+. Calc'd for C19H12BrFN4OS: 441.99.

Workup

  1. customA pressure reaction vessel
  2. temperatureAfter cooling for rt
  3. customreaction
  4. temperaturewas heated at 100° C. for another 30 min
  5. temperatureAfter cooling for rt
  6. customthe organic layer was separated with a separatory funnel
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto afford yellow oil which
  11. customwas purified with reverse phase HPLC
  12. additionFractions containing product
  13. concentrationwere concentrated
  14. additionsaturated aq. NaHCO3 (25 mL) was added
  15. customA white solid precipitated out of solution which
  16. filtrationwas filtered off
  17. customdried

Sources & evidence

ORD record
ord-3f23e37d32504746afbfc9461b5f03b7
Source dataset
uspto-grants-2014_11
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08883782B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes