Acetic Acid → 1-({4-[2-(1-oxo-1,3-dihydro-2-benzofuran-5-yl)ethyl]piperazin-1-yl}methyl)-3,4-dihydro-1H-isochromene-5-carbonitrile

HRID 1187135Notes

Reaction equation

HRID 1187135 reaction equation
[CH:1]([CH:3]1[C:12]2[CH:11]=[CH:10][CH:9]=[C:8]([C:13]#[N:14])[C:7]=2[CH2:6][CH2:5][O:4]1)=O.Cl.[N:16]1([CH2:22][CH2:23][C:24]2[CH:33]=[CH:32][C:27]3[C:28](=[O:31])[O:29][CH2:30][C:26]=3[CH:25]=2)[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]1.CCN(C(C)C)C(C)C.CC(O)=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)Cl.O>[O:31]=[C:28]1[C:27]2[CH:32]=[CH:33][C:24]([CH2:23][CH2:22][N:16]3[CH2:21][CH2:20][N:19]([CH2:1][CH:3]4[C:12]5[CH:11]=[CH:10][CH:9]=[C:8]([C:13]#[N:14])[C:7]=5[CH2:6][CH2:5][O:4]4)[CH2:18][CH2:17]3)=[CH:25][C:26]=2[CH2:30][O:29]1

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 81531DiisopropylethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 595686551-formyl-3,4-dihydro-1H-isochromene-5-carbonitrileHCID 666467325-(2-piperazin-1-ylethyl)-2-benzofuran-1(3H)-one hydrochloride

Product 1

HCID 498016261-({4-[2-(1-oxo-1,3-dihydro-2-benzofuran-5-yl)ethyl]piperazin-1-yl}methyl)-3,4-dihydro-1H-isochromene-5-carbonitrile

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 1-formyl-3,4-dihydro-1H-isochromene-5-carbonitrile (65 mg, 0.35 mmol), 5-(2-piperazin-1-ylethyl)-2-benzofuran-1(3H)-one hydrochloride (100 mg, 0.35 mmol), DIEA (45 mg, 0.35 mmol), AcOH (21 mg, 0.35 mmol) in 3 mL of DCM was stirred 30 min at room temperature and then NaBH(OAc)3 (440 mg, 2.1 mmol) was added. The mixture was stirred over night at room temperature. Water was added and the mixture was extracted with DCM. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, concentrated and the residue was purified by prep-HPLC to give 1-({4-[2-(1-oxo-1,3-dihydro-2-benzofuran-5-yl)ethyl]piperazin-1-yl}methyl)-3,4-dihydro-1H-isochromene-5-carbonitrile.

Workup

  1. stirringThe mixture was stirred over night at room temperature
  2. extractionthe mixture was extracted with DCM
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over anhydrous Na2SO4
  5. concentrationconcentrated
  6. customthe residue was purified by prep-HPLC

Sources & evidence

ORD record
ord-be362a1f7368416aa3576e2c695ac924
Source dataset
uspto-grants-2014_03
Patent number
US08673920B2

Reaction notes

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