Water → HCID 57827445, compound

HRID 1693257Notes

Reaction equation

HRID 1693257 reaction equation
[C:1]([C:3]1[CH:4]=[C:5](B(O)O)[CH:6]=[N:7][CH:8]=1)#[N:2].C(=O)([O-])[O-].[Na+].[Na+].C(OC([N:25]([C:33]1[S:34][CH2:35][C@@H:36]2[CH2:41][CH2:40][CH2:39][C@:37]2([C:42]2[CH:47]=[C:46](Br)[CH:45]=[CH:44][C:43]=2[F:49])[N:38]=1)C(OC(C)(C)C)=O)=O)(C)(C)C.O>CN(C=O)C.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>[NH2:25][C:33]1[S:34][CH2:35][C@@H:36]2[CH2:41][CH2:40][CH2:39][C@:37]2([C:42]2[CH:47]=[C:46]([C:5]3[CH:6]=[N:7][CH:8]=[C:3]([CH:4]=3)[C:1]#[N:2])[CH:45]=[CH:44][C:43]=2[F:49])[N:38]=1

Participants

7

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 450795765-Cyanopyridine-3-boronic acidHCID 57827441HCID 57827441, compound

Product 1

HCID 57827445HCID 57827445, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

5-Cyano-3-pyridinylboronic acid (37.9 mg), tetrakis(triphenylphosphine)palladium and a 1 N sodium carbonate solution (256 μL) were added to a solution of (±)-N,N-bis(tert-butoxycarbonyl) [(4aR*,7aS*)-7a-(5-bromo-2-fluorophenyl)-4,4a,5,6,7,7a-hexahydrocyclopenta[d][1,3]thiazin-2-yl]amine (70.0 mg) in DMF (5 mL). After replacement with nitrogen, the mixture was stirred at 80° C. for two hours. After cooling to room temperature, water was added to the reaction mixture. The aqueous layer was extracted with ethyl acetate, and the organic layer was washed with water and brine. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was dissolved in dichloromethane (3 mL). Trifluoroacetic acid (1 mL) was added and the mixture was stirred at room temperature for two hours. The reaction mixture was diluted with water, followed by neutralization with a saturated sodium bicarbonate solution. The aqueous layer was extracted with ethyl acetate, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by NH-silica gel column chromatography to obtain the title compound.

Workup

  1. temperatureAfter cooling to room temperature
  2. extractionThe aqueous layer was extracted with ethyl acetate
  3. washthe organic layer was washed with water and brine
  4. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  5. customthe solvent was evaporated under reduced pressure
  6. dissolutionThe residue was dissolved in dichloromethane (3 mL)
  7. additionTrifluoroacetic acid (1 mL) was added
  8. stirringthe mixture was stirred at room temperature for two hours
  9. additionThe reaction mixture was diluted with water
  10. extractionThe aqueous layer was extracted with ethyl acetate
  11. dry with materialthe organic layer was dried over anhydrous magnesium sulfate
  12. customThe solvent was evaporated under reduced pressure
  13. customthe residue was purified by NH-silica gel column chromatography

Sources & evidence

ORD record
ord-654ec098ab4249c186c9d253a64ac2a6
Source dataset
uspto-grants-2012_04
Patent number
US08158620B2

Reaction notes

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