Methanol → 3-(1-Isopropyltriazol-4-yl)-5-[3-methyl-4-(morpholinomethyl)phenyl]pyridin-2-amine

HRID 1053139Notes

Reaction equation

HRID 1053139 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([N:16]3[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)=O)=[C:10]([CH3:22])[CH:9]=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>[CH:28]([N:26]1[CH:27]=[C:23]([C:3]2[C:2]([NH2:1])=[N:7][CH:6]=[C:5]([C:8]3[CH:13]=[CH:12][C:11]([CH2:14][N:16]4[CH2:17][CH2:18][O:19][CH2:20][CH2:21]4)=[C:10]([CH3:22])[CH:9]=3)[CH:4]=2)[N:24]=[N:25]1)([CH3:30])[CH3:29]

Participants

6

Reactant 3

HCID 887MethanolHCID 4311764Sodium borohydrideHCID 77106367[4-[6-Amino-5-(1-isopropyltriazol-4-yl)-3-pyridyl]-2-methyl-phenyl]-morpholino-methanone

Product 1

HCID 771063683-(1-Isopropyltriazol-4-yl)-5-[3-methyl-4-(morpholinomethyl)phenyl]pyridin-2-amineYield 16.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

BF3Et2O in THF (47-49%) (0.87 mL, 2.46 mmol) was added to a solution of [4-[6-amino-5-(1-isopropyltriazol-4-yl)-3-pyridyl]-2-methyl-phenyl]-morpholino-methanone (200 mg, 0.46 mmol) in THF (10.0 mL) at 0° C. The reaction mixture was stirred for 30 min, NaBH4 (93.5 mg, 2.46 mmol) was added at 0° C., reaction mixture was slowly warmed to RT, stirred for 16 h. Reaction mixture was again cooled to 0° C., added MeOH (5.0 mL) and 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. Product was further purified by Prep.HPLC furnished 30 mg (Yield: 15.5%) of the title compound as a white solid.

Workup

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

Sources & evidence

ORD record
ord-f7a1fa1442914d92a21fb1adfa489e57
Source dataset
uspto-grants-2016_07
Patent number
US09393248B1

Reaction notes

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