Dimethylformamide → (S)-3-(3,3-dimethylbut-1-ynyl)-7-(pyridin-3-yl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazol]-2'-amine

HRID 335699Notes

Reaction equation

HRID 335699 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C@:15]3([CH2:19][O:18][C:17]([NH2:20])=[N:16]3)[C:14]3[C:9](=[CH:10][CH:11]=[C:12]([C:21]4[CH:22]=[N:23][CH:24]=[CH:25][CH:26]=4)[CH:13]=3)[O:8][C:5]2=[N:6][CH:7]=1.C(NC(C)C)(C)C.[CH3:34][C:35]([CH3:39])([CH3:38])[C:36]#[CH:37].CN(C=O)C>O.[Cu](I)I.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.C(OCC)(=O)C>[CH3:34][C:35]([CH3:39])([CH3:38])[C:36]#[C:37][C:2]1[CH:3]=[C:4]2[C@:15]3([CH2:19][O:18][C:17]([NH2:20])=[N:16]3)[C:14]3[C:9](=[CH:10][CH:11]=[C:12]([C:21]4[CH:22]=[N:23][CH:24]=[CH:25][CH:26]=4)[CH:13]=3)[O:8][C:5]2=[N:6][CH:7]=1

Participants

9

Reactant 4

HCID 6228DimethylformamideHCID 7912DiisopropylamineHCID 135123,3-Dimethyl-1-butyneHCID 67241561(5S)-3-bromo-7-(3-pyridinyl)spiro[chromeno[2,3-b]pyridine-5,4'-[1,3]oxazol]-2'-amine

Product 1

HCID 45256651(S)-3-(3,3-dimethylbut-1-ynyl)-7-(pyridin-3-yl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazol]-2'-amineYield 64.6%

Reagents, catalysts & solvents 4

HCID 83717Copper iodideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

(5S)-3-Bromo-7-(3-pyridinyl)spiro[chromeno[2,3-b]pyridine-5,4′-[1,3]oxazol]-2′-amine (170 mg, 0.415 mmol), diisopropyl amine (2911 μL, 20.77 mmol), copper iodide (15.82 mg, 0.083 mmol), tetrakis(triphenylphosphine)palladium (48.0 mg, 0.042 mmol), 3,3-dimethylbut-1-yne (171 mg, 2.082 mmol) and DMF (2769 μL, 0.415 mmol) were combined in a sealable tube, which was then flushed with argon and heated at 90° C. for 5 hours. After cooling to room temperature the reaction in the tube was diluted with water (25 mL) and poured into a separatory funnel containing ethyl acetate (25 mL). The layers were separated and the aqueous layer was extracted with ethyl acetate (4×50 mL). The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo to provide a brown oil that was purified by silica gel chromatography (Redi-Sep pre-packed silica gel column (40 g), 0-10% methanol in methylenechloride with 0.1% ammonium hydroxide) to provide (5S)-3-(3,3-dimethyl-1-butyn-1-yl)-7-(3-pyridinyl)spiro[chromeno[2,3-b]pyridine-5,4′-[1,3]oxazol]-2′-amine (110 mg, 0.268 mmol, 64.5% yield) as a brown foam. MS m/z=411.2 [M+H]+. Calc'd for C25H23N4O3: 411.2.

Workup

  1. customwhich was then flushed with argon
  2. temperatureAfter cooling to room temperature
  3. customthe reaction in the tube
  4. additionpoured into a separatory funnel
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted with ethyl acetate (4×50 mL)
  7. washThe combined organic layers were washed with brine
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customto provide a brown oil that
  12. customwas purified by silica gel chromatography (Redi-Sep pre-packed silica gel column (40 g), 0-10% methanol in methylenechloride with 0.1% ammonium hydroxide)

Sources & evidence

ORD record
ord-a97bb6b86a9348318559e3d524fcd790
Source dataset
uspto-grants-2014_11
Patent number
US08883782B2

Reaction notes

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