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 1474392Notes

Reaction equation

HRID 1474392 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-970874e137434382927c277bb81c5bfe
Source dataset
uspto-grants-2015_04
Patent number
US09018211B2

Reaction notes

Loading…