Triphenylphosphine → 2-(((5-Chloropyrido[3,4-b]pyrazin-2-yl)oxy)methyl)-5-methyloxazole

HRID 627717Notes

Reaction equation

HRID 627717 reaction equation
[Cl:1][C:2]1[C:7]2=[N:8][CH:9]=[C:10]([OH:12])[N:11]=[C:6]2[CH:5]=[CH:4][N:3]=1.[CH3:13][C:14]1[O:18][C:17]([CH2:19]O)=[N:16][CH:15]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>O1CCCC1>[Cl:1][C:2]1[C:7]2=[N:8][CH:9]=[C:10]([O:12][CH2:19][C:17]3[O:18][C:14]([CH3:13])=[CH:15][N:16]=3)[N:11]=[C:6]2[CH:5]=[CH:4][N:3]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 22081028(5-Methyl-1,3-oxazol-2-yl)methanolHCID 178516729HCID 178516729, compound

Product 1

HCID 867281542-(((5-Chloropyrido[3,4-b]pyrazin-2-yl)oxy)methyl)-5-methyloxazoleYield 79%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 5-chloropyrido[3,4-b]pyrazin-2-ol (200 mg, 1.1 mmol) and (5-methyloxazol-2-yl)methanol (187 mg, 1.6 mmol) in tetrahydrofuran (5 mL) was added triphenylphosphine (433 mg, 1.6 mmol). The reaction mixture was cooled to 0° C. and diisopropyl azodicarboxylate (0.33 mL, 1.6 mmol) was added slowly. The reaction was stirred at 0° C. for 1 hour, and then allowed to warm to ambient temperature overnight. After 16 hours, the reaction was quenched with water and extracted into ethyl acetate. The organic layer was concentrated, and the crude product was purified by column chromatography, eluting with 20-80% (3:1 ethyl acetate/ethanol) in heptane. The less-polar isomer was isolated to provide the title compound (120 mg, 0.43 mmol, 79% yield) as a white solid. LC/MS (ESI+) m/z: 277.0 (M+H+).

Workup

  1. temperatureto warm to ambient temperature overnight
  2. waitAfter 16 hours
  3. customthe reaction was quenched with water
  4. extractionextracted into ethyl acetate
  5. concentrationThe organic layer was concentrated
  6. customthe crude product was purified by column chromatography
  7. washeluting with 20-80% (3:1 ethyl acetate/ethanol) in heptane
  8. customThe less-polar isomer was isolated

Sources & evidence

ORD record
ord-754229f9b61c402689b1bccf2746d67d
Source dataset
uspto-grants-2016_04
Patent number
US09309263B2

Reaction notes

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