Acetic Acid → 2-(4-Cyclopropylpiperazin-1-yl)-5-pyrrolidin-1-ylmethylbenzooxazole

HRID 1944703Notes

Reaction equation

HRID 1944703 reaction equation
[CH:1]1([N:4]2[CH2:9][CH2:8][N:7]([C:10]3[O:11][C:12]4[CH:18]=[CH:17][C:16]([CH:19]=O)=[CH:15][C:13]=4[N:14]=3)[CH2:6][CH2:5]2)[CH2:3][CH2:2]1.[NH:21]1[CH2:25][CH2:24][CH2:23][CH2:22]1.C(O)(=O)C.[BH3-]C#N.[Na+]>CO.C1COCC1>[CH:1]1([N:4]2[CH2:9][CH2:8][N:7]([C:10]3[O:11][C:12]4[CH:18]=[CH:17][C:16]([CH2:19][N:21]5[CH2:25][CH2:24][CH2:23][CH2:22]5)=[CH:15][C:13]=4[N:14]=3)[CH2:6][CH2:5]2)[CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 31268PyrrolidineHCID 5003444Sodium cyanoborohydrideHCID 595887962-(4-Cyclopropylpiperazin-1-yl)benzooxazole-5-carboxaldehyde

Product 1

HCID 237289312-(4-Cyclopropylpiperazin-1-yl)-5-pyrrolidin-1-ylmethylbenzooxazoleYield 40%

Reagents, catalysts & solvents 1

HCID 21899815MeOH tetrahydrofuranSolvent

Procedure

To a solution of 2-(4-cyclopropylpiperazin-1-yl)benzooxazole-5-carboxaldehyde (400 mg, 1.48 mmol) and pyrrolidine (210 mg, 2.96 mmol) in CH3OH/THF (36 mL, 1:3) was added acetic acid (142 mg, 2.37 mmol), followed by NaCNBH3 (137 mg, 2.37 mmol). The mixture was heated at reflux for 12 h. The volatiles were removed and the residue was diluted with water (5 mL). The resulting mixture was extracted with CH2Cl2 (3×10 mL) and the combined organic extracts were dried (Na2SO4) and concentrated. The residue was purified by column chromatography on silica gel (elute: 2% dichloromethane in methanol) to give 193 mg (40%) of 2-(4-cyclopropylpiperazin-1-yl)-5-pyrrolidin-1-ylmethylbenzooxazole.

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 12 h
  3. customThe volatiles were removed
  4. additionthe residue was diluted with water (5 mL)
  5. extractionThe resulting mixture was extracted with CH2Cl2 (3×10 mL)
  6. dry with materialthe combined organic extracts were dried (Na2SO4)
  7. concentrationconcentrated
  8. customThe residue was purified by column chromatography on silica gel (elute: 2% dichloromethane in methanol)

Sources & evidence

ORD record
ord-5a7ef58419cf4688b0600b10f419a3b0
Source dataset
uspto-grants-2013_03
Patent number
US08394842B2

Reaction notes

Loading…