Trimethyl borate → 2-(4-Amino-1,2,5-oxadiazol-3-yl)-4-chloro-1-ethyl-1H-imidazo[4,5-c]pyridin-7-ol

HRID 1863999Notes

Reaction equation

HRID 1863999 reaction equation
Br[C:2]1[C:3]2[N:11]([CH2:12][CH3:13])[C:10]([C:14]3[C:15]([NH2:19])=[N:16][O:17][N:18]=3)=[N:9][C:4]=2[C:5]([Cl:8])=[N:6][CH:7]=1.C([Mg]Cl)(C)C.B(OC)(OC)[O:26]C.C(=O)=O.CC(C)=O>C1COCC1>[NH2:19][C:15]1[C:14]([C:10]2[N:11]([CH2:12][CH3:13])[C:3]3[C:2]([OH:26])=[CH:7][N:6]=[C:5]([Cl:8])[C:4]=3[N:9]=2)=[N:18][O:17][N:16]=1

Participants

6

Reactant 4

HCID 8470Trimethyl borateHCID 112908584-(7-Bromo-4-chloro-1-ethyl-1H-imidazo[4,5-c]pyridin-2-yl)-1,2,5-oxadiazol-3-amineHCID 18522661Acetone cardiceHCID 178418918HCID 178418918, compound

Product 1

HCID 579738952-(4-Amino-1,2,5-oxadiazol-3-yl)-4-chloro-1-ethyl-1H-imidazo[4,5-c]pyridin-7-olYield 91.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A suspension of 4-(7-bromo-4-chloro-1-ethyl-1H-imidazo[4,5-c]pyridin-2-yl)-1,2,5-oxadiazol-3-amine (VI, 50 g, 0.14 mol) in THF (1 L) was cooled in a dry-ice/acetone bath until the internal temperature was below −75° C. Isopropyl magnesium chloride (225 mL, 2M in ether, 0.45 mol) was added slowly at a rate to keep the reaction temperature below −70° C. After an additional 10 min., trimethyl borate (54 mL, 0.48 mol) was added and the reaction was maintained in the dry-ice acetone bath for 1 h. The bath was removed and the reaction was allowed to reach ambient temperature. After 18 h., the resultant yellow suspension was cooled to 0° C. A solution of 30% hydrogen peroxide (250 mL) and 3N NaOH (100 mL) was added at a rate to keep the reaction temperature below 40° C. The ice bath was then removed and the reaction was stirred vigorously at ambient temperature for 2 h. The bulk of the organic solvent was removed under reduced pressure and the aqueous layer was acidified to pH 3 with 1N HCl. After stirring the resulting suspension for 30 min., ethyl acetate (200 mL) was added. After stirring for another 1 h, the solid was collected by filtration. The filter cake was washed sequentially with water, ethyl acetate, toluene and ethyl acetate. The solid was dried to a constant weight to give 35.9 g (88% yield) of the desired compound (VII) as a pale yellow solid. This was used without further purification. MS (ES+) m/z 281.3 (M+H)+.

Workup

  1. temperaturewas cooled in a dry-ice/acetone bath until the internal temperature
  2. customwas below −75° C
  3. customthe reaction temperature below −70° C
  4. customThe bath was removed
  5. customto reach ambient temperature
  6. waitAfter 18 h.
  7. additionA solution of 30% hydrogen peroxide (250 mL) and 3N NaOH (100 mL) was added at a rate
  8. customthe reaction temperature below 40° C
  9. customThe ice bath was then removed
  10. customThe bulk of the organic solvent was removed under reduced pressure
  11. stirringAfter stirring the resulting suspension for 30 min.
  12. additionethyl acetate (200 mL) was added
  13. stirringAfter stirring for another 1 h
  14. filtrationthe solid was collected by filtration
  15. washThe filter cake was washed sequentially with water, ethyl acetate, toluene and ethyl acetate
  16. customThe solid was dried to a constant weight

Sources & evidence

ORD record
ord-d9d58981e1f44daeb401e2450b953593
Source dataset
uspto-grants-2009_12
Patent number
US07625890B2

Reaction notes

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