Carbonic acid--N,N-diethylethanamine (1/2) → 5-{(1R)-1-hydroxy-2-[(3R)-3-{[(2R)-2-hydroxy-2-(4-methyl-1-oxo-1,3-dihydro-2-benzofuran-5-yl)ethyl]amino}pyrrolidin-1-yl]ethyl}-4-methyl-2-benzofuran-1(3H)-one

HRID 515116Notes

Reaction equation

HRID 515116 reaction equation
Cl.[NH2:2][C@@H:3]1[CH2:7][CH2:6][N:5]([CH2:8][C@@H:9]([C:11]2[CH:20]=[CH:19][C:14]3[C:15](=[O:18])[O:16][CH2:17][C:13]=3[C:12]=2[CH3:21])[OH:10])[CH2:4]1.[CH3:22][C:23]1[C:31]2[CH2:30][O:29][C:28](=[O:32])[C:27]=2[CH:26]=[CH:25][C:24]=1[C@@H:33]1[CH2:35][O:34]1.CC[NH+](CC)CC.CC[NH+](CC)CC.C([O-])([O-])=O>C(O)C>[OH:10][C@H:9]([C:11]1[CH:20]=[CH:19][C:14]2[C:15](=[O:18])[O:16][CH2:17][C:13]=2[C:12]=1[CH3:21])[CH2:8][N:5]1[CH2:6][CH2:7][C@@H:3]([NH:2][CH2:35][C@H:33]([OH:34])[C:24]2[CH:25]=[CH:26][C:27]3[C:28](=[O:32])[O:29][CH2:30][C:31]=3[C:23]=2[CH3:22])[CH2:4]1

Participants

5

Reactant 3

HCID 15264167Carbonic acid--N,N-diethylethanamine (1/2)HCID 595686464-Methyl-5-((2R)-oxiran-2-yl)-2-benzofuran-1(3H)-one2×HCID 901903035-{(1R)-2-[(3R)-3-aminopyrrolidin-1-yl]-1-hydroxyethyl}-4-methyl-2-benzofuran-1(3H)-one hydrochloride2×

Product 1

HCID 904099855-{(1R)-1-hydroxy-2-[(3R)-3-{[(2R)-2-hydroxy-2-(4-methyl-1-oxo-1,3-dihydro-2-benzofuran-5-yl)ethyl]amino}pyrrolidin-1-yl]ethyl}-4-methyl-2-benzofuran-1(3H)-one

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A microwave vial was charged with 5-{(1R)-2-[(3R)-3-aminopyrrolidin-1-yl]-1-hydroxyethyl}-4-methyl-2-benzofuran-1(3H)-one hydrochloride [INTERMEDIATE 4] (100 mg, 0.32 mmol), 4-methyl-5-[(2R)-oxiran-2-yl]-2-benzofuran-1(3H)-one [INTERMEDIATE 2B] (61 mg, 0.32 mmol), MP-carbonate resin (200 mg), and ethanol (1 mL). The reaction mixture was heated in a microwave reactor at 150 C for 1 hour, and then cooled, filtered and concentrated in vacuo. The resulting residue was dissolved in DMSO (1 mL) and purified by HPLC to provide 5-{(1R)-1-hydroxy-2-[(3R)-3-{[(2R)-2-hydroxy-2-(4-methyl-1-oxo-1,3-dihydro-2-benzofuran-5-yl)ethyl]amino}pyrrolidin-1-yl]ethyl}-4-methyl-2-benzofuran-1(3H)-one.

Workup

  1. temperatureThe reaction mixture was heated in a microwave reactor at 150 C for 1 hour
  2. temperaturecooled
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. dissolutionThe resulting residue was dissolved in DMSO (1 mL)
  6. custompurified by HPLC

Sources & evidence

ORD record
ord-f08add80473942d4b85baf8aeb12ae58
Source dataset
uspto-grants-2015_08
Patent number
US09108947B2

Reaction notes

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