Diisopropylethylamine → 4-{2-[5-(2-Pyrrolidin-1-ylethoxy)benzofuran-2-carbonylamino]-ethoxy}-benzoic acid methyl ester

HRID 29709

Reaction equation

HRID 29709 reaction equation
[N:1]1([CH2:6][CH2:7][O:8][C:9]2[CH:10]=[CH:11][C:12]3[O:16][C:15]([C:17]([OH:19])=O)=[CH:14][C:13]=3[CH:20]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.Cl.[CH3:22][O:23][C:24](=[O:35])[C:25]1[CH:30]=[CH:29][C:28]([O:31][CH2:32][CH2:33][NH2:34])=[CH:27][CH:26]=1.C(N(C(C)C)CC)(C)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>CN(C=O)C>[CH3:22][O:23][C:24](=[O:35])[C:25]1[CH:26]=[CH:27][C:28]([O:31][CH2:32][CH2:33][NH:34][C:17]([C:15]2[O:16][C:12]3[CH:11]=[CH:10][C:9]([O:8][CH2:7][CH2:6][N:1]4[CH2:2][CH2:3][CH2:4][CH2:5]4)=[CH:20][C:13]=3[CH:14]=2)=[O:19])=[CH:29][CH:30]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 229283195-(2-Pyrrolidin-1-ylethoxy)benzofuran-2-carboxylic acidHCID 50988568Methyl 4-(2-aminoethoxy)benzoate hydrochloride

Product 1

HCID 666881644-{2-[5-(2-Pyrrolidin-1-ylethoxy)benzofuran-2-carbonylamino]-ethoxy}-benzoic acid methyl esterYield 76.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 5-(2-pyrrolidin-1-ylethoxy)benzofuran-2-carboxylic acid (156 mg, 0.50 mmol) and 4-(2-aminoethoxy)benzoic acid methyl ester hydrochloride (129 mg, 0.56 mmol) in DMF (4.5 ml) in a 20 ml vial was added diisopropylethylamine (0.88 ml, 5.1 mmol). A solution of O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (740 μL, 0.82 M, 0.61 mmol) in DMF was added to give a bright yellow solution. The vial was purged with nitrogen and stirred at room temperature for 18 h. The solution was removed and the residue was dissolved in EtOAc (25 ml) and washed with H2O, 1.0M aqueous K2CO3, and brine. The organic layer was dried over anhydrous MgSO4 and solvent was removed on a rotary evaporator. Purification of the residue by column chromatography on a silica gel column using 93:5:2 CH2Cl2:MeOH:TEA eluent provided 4-{2-[5-(2-pyrrolidin-1-ylethoxy)benzofuran-2-carbonylamino]-ethoxy}-benzoic acid methyl ester as a beige solid (174 mg).

Workup

  1. customto give a bright yellow solution
  2. customThe vial was purged with nitrogen
  3. customThe solution was removed
  4. dissolutionthe residue was dissolved in EtOAc (25 ml)
  5. washwashed with H2O, 1.0M aqueous K2CO3, and brine
  6. dry with materialThe organic layer was dried over anhydrous MgSO4 and solvent
  7. customwas removed on a rotary evaporator
  8. customPurification of the residue by column chromatography on a silica gel column

Sources & evidence

ORD record
ord-456f2ac7c960459c823ee108066d4c20
Source dataset
uspto-grants-2008_09
Patent number
US07420089B2

Linked notes

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