Acetic Acid → [2-(4-Cyclopropylpiperazin-1-yl)benzooxazol-5-ylmethyl]dimethylamine

HRID 1944704Notes

Reaction equation

HRID 1944704 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.Cl.[CH3:22][NH:23][CH3:24].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:23]([CH3:24])[CH3:22])=[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 10473Dimethylamine, hydrochlorideHCID 5003444Sodium cyanoborohydrideHCID 595887962-(4-Cyclopropylpiperazin-1-yl)benzooxazole-5-carboxaldehyde

Product 1

HCID 23728932[2-(4-Cyclopropylpiperazin-1-yl)benzooxazol-5-ylmethyl]dimethylamineYield 60.1%

Reagents, catalysts & solvents 1

HCID 21899815MeOH tetrahydrofuranSolvent

Procedure

To a solution of 2-(4-cyclopropylpiperazin-1-yl)benzooxazole-5-carboxaldehyde (350 mg, 1.29 mmol) and dimethylamine hydrochloride (210 mg, 2.58 mmol) in CH3OH/THF (32 mL, 1:3) was added acetic acid (124 mg, 2.06 mmol), followed by NaCNBH3 (120 mg, 2.06 mmol). The mixture was heated at reflux for 12 h. The volatiles were removed under reduced pressure and the residue was diluted with water (5 mL). The mixture was extracted with CH2Cl2 (3×10 mL) and the combined organic extracts were dried (Na2SO4) and concentrated. The residue was purified by the preparative HPLC to give 233 mg (60%) of [2-(4-cyclopropylpiperazin-1-yl)benzooxazol-5-ylmethyl]dimethylamine as a trifluoroacetate salt.

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 12 h
  3. customThe volatiles were removed under reduced pressure
  4. additionthe residue was diluted with water (5 mL)
  5. extractionThe 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 the preparative HPLC

Sources & evidence

ORD record
ord-02dd4833bd094d159a92625507b3aee0
Source dataset
uspto-grants-2013_03
Patent number
US08394842B2

Reaction notes

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