Diisopropylethylamine → (3S)-6-(1-Hydroxy-2-((1S,4S)-5-((R)-2-hydroxy-2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)ethyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)ethyl)-3-methylisochroman-1-one

HRID 2281356Notes

Reaction equation

HRID 2281356 reaction equation
[C@H:1]12[CH2:7][C@H:4]([NH:5][CH2:6]1)[CH2:3][N:2]2[CH2:8][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])[OH:10].[CH3:22][C@H:23]1[CH2:32][C:31]2[C:26](=[CH:27][CH:28]=[C:29]([CH:33]3[CH2:35][O:34]3)[CH:30]=2)[C:25](=[O:36])[O:24]1.CCN(C(C)C)C(C)C>C(O)C>[OH:34][CH:33]([C:29]1[CH:30]=[C:31]2[C:26](=[CH:27][CH:28]=1)[C:25](=[O:36])[O:24][C@@H:23]([CH3:22])[CH2:32]2)[CH2:35][N:5]1[CH2:6][C@@H:1]2[CH2:7][C@H:4]1[CH2:3][N:2]2[CH2:8][C@H:9]([OH:10])[C:11]1[C:12]([CH3:21])=[C:13]2[C:14](=[CH:19][CH:20]=1)[C:15](=[O:18])[O:16][CH2:17]2

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 86693038(3S)-3-Methyl-6-(oxiran-2-yl)-3,4-dihydro-1H-isochromen-1-one2×HCID 1176420455-{(1R)-2-[(1S,4S)-2,5-Diazabicyclo[2.2.1]hept-2-yl]-1-hydroxyethyl}-4-methyl-2-benzofuran-1 (3H)-one2×

Product 1

HCID 71557998(3S)-6-(1-Hydroxy-2-((1S,4S)-5-((R)-2-hydroxy-2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)ethyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)ethyl)-3-methylisochroman-1-one

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 5-{(1R)-2-[(1S,4S)-2,5-diazabicyclo[2.2.1]hept-2-yl]-1-hydroxyethyl}-4-methyl-2-benzofuran-1(3H)-one [INTERMEDIATE 36](100 mg, 0.35 mmol) in ethanol (2 mL) was added (3S)-3-methyl-6-(oxiran-2-yl)-3,4-dihydro-1H-isochromen-1-one (INTERMEDIATE 24) (71 mg, 0.35 mmol) and Hunig's base (61 uL, 0.35 mmol). The mixture was heated to 80° C. for 20 hours. The solvent was removed using rotary evaporation and the crude oil was purified via by silica gel chromatography (0-7% MeOH in DCM) to yield the pure respective diastereomers as a faster eluting isomer D1 (LCMS: m/z 493.2 (M+H)+) and slower eluting diastereomer D2 (LCMS: m/z 493.2 (M+H)+).

Workup

  1. customThe solvent was removed
  2. customevaporation
  3. customthe crude oil was purified via by silica gel chromatography (0-7% MeOH in DCM)
  4. customto yield the pure respective diastereomers as
  5. washa faster eluting isomer D1 (LCMS: m/z 493.2 (M+H)+)
  6. washslower eluting diastereomer D2 (LCMS: m/z 493.2 (M+H)+)

Sources & evidence

ORD record
ord-f79c167ec8b94f96ad565c0a03945136
Source dataset
uspto-grants-2015_09
Patent number
US09139585B2

Reaction notes

Loading…