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

HRID 1970415Notes

Reaction equation

HRID 1970415 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]=[N:25][CH:26]=4)[CH:13]=3)[O:8][C:5]2=[N:6][CH:7]=1.CN(C=O)C.[CH3:32][C:33]([CH3:37])([CH3:36])[C:34]#[CH:35].C(OCC)(=O)C>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.[Cu]I>[CH3:32][C:33]([CH3:37])([CH3:36])[C:34]#[C:35][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:26]=[N:25][CH:24]=[N:23][CH:22]=4)[CH:13]=3)[O:8][C:5]2=[N:6][CH:7]=1

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 8857Ethyl AcetateHCID 135123,3-Dimethyl-1-butyneHCID 67241433(S)-3-bromo-7-(pyrimidin-5-yl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazol]-2'-amine

Product 1

HCID 45256655(S)-3-(3,3-dimethylbut-1-ynyl)-7-(pyrimidin-5-yl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazol]-2'-amine

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

Combined (S)-3-bromo-7-(pyrimidin-5-yl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-2′-amine (120 mg, 0.293 mmol), tetrakis(triphenylphosphine)palladium (33.8 mg, 0.029 mmol), copper(i) iodide (11.14 mg, 0.059 mmol) and DMF (1950 μL, 0.293 mmol). Added 3,3-dimethylbut-1-yne (96 mg, 1.170 mmol) and DIPA (2085 μL, 14.63 mmol), flushed with argon, sealed and heated at 90° C. overnight. The reaction 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 (2×50 mL). The combined organic layers were washed with water, 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 (12 g), 0-10% methanol in DCM with 0.1% ammonium hydroxide) to provide (S)-3-(3,3-dimethylbut-1-ynyl)-7-(pyrimidin-5-yl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-2′-amine as a tan solid. Found MS: MH+=412.2.

Workup

  1. customsealed
  2. additionpoured into a separatory funnel
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with ethyl acetate (2×50 mL)
  5. washThe combined organic layers were washed with water
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto provide a brown oil that
  10. customwas purified by silica gel chromatography (Redi-Sep pre-packed silica gel column (12 g), 0-10% methanol in DCM with 0.1% ammonium hydroxide)

Sources & evidence

ORD record
ord-a374d3fcb9dc4a04968fae1f2692a188
Source dataset
uspto-grants-2013_04
Patent number
US08426447B2

Reaction notes

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