Methanol → HCID 77106562, compound

HRID 1053144Notes

Reaction equation

HRID 1053144 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[CH:9]=[C:10]([C:15]([N:17]3[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)=O)[CH:11]=[C:12]([Cl:14])[CH:13]=2)=[CH:4][C:3]=1[C:23]1[N:24]=[N:25][N:26]([CH:28]([CH3:30])[CH3:29])[CH:27]=1.[BH4-].[Na+].CO>C1COCC1.O>[Cl:14][C:12]1[CH:13]=[C:8]([C:5]2[CH:4]=[C:3]([C:23]3[N:24]=[N:25][N:26]([CH:28]([CH3:30])[CH3:29])[CH:27]=3)[C:2]([NH2:1])=[N:7][CH:6]=2)[CH:9]=[C:10]([CH2:15][N:17]2[CH2:18][CH2:19][O:20][CH2:21][CH2:22]2)[CH:11]=1

Participants

6

Reactant 3

HCID 887MethanolHCID 4311764Sodium borohydrideHCID 77106561HCID 77106561, compound

Product 1

HCID 77106562HCID 77106562, compoundYield 20.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

BF3Et2O in THF (47-49%) (0.70 mL, 2.34 mmol) was added to a solution of [3-[6-amino-5-(1-isopropyltriazol-4-yl)-3-pyridyl]-5-chloro-phenyl]-morpholino-methanone (200 mg, 0.46 mmol) in THF (10.0 mL) at 0° C., then reaction mixture was stirred for 30 min, added NaBH4 (89 mg, 2.36 mmol) at 0° C., reaction mixture was slowly warmed to RT, stirred for 16 h. Reaction mixture was cooled to 0° C., added MeOH (5.0 mL) to the reaction mixture, heated to 70° C. for 2 h. The reaction mixture was diluted with water (50 mL) and extracted with ethyl acetate (2×30 mL). Combined organic layers was dried over Na2SO4 and concentrated under reduced pressure. Crude product was purified by silica (100-200 mesh) column eluted with 2% MeOH in DCM to afford 39 mg (Yield: 20.2%) of the title compound. This was converted to its HCl salt by using HCl in ether (2M) to afford 45 mg as a pale gray solid.

Workup

  1. customreaction mixture
  2. customreaction mixture
  3. stirringstirred for 16 h
  4. customReaction mixture
  5. temperaturewas cooled to 0° C.
  6. temperatureheated to 70° C. for 2 h
  7. extractionextracted with ethyl acetate (2×30 mL)
  8. dry with materialCombined organic layers was dried over Na2SO4
  9. concentrationconcentrated under reduced pressure
  10. customCrude product was purified by silica (100-200 mesh) column
  11. washeluted with 2% MeOH in DCM

Sources & evidence

ORD record
ord-eecb26df08454409869dab57a917fc90
Source dataset
uspto-grants-2016_07
Patent number
US09393248B1

Reaction notes

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