(3S)-3-Methyl-6-(oxiran-2-yl)-3,4-dihydro-1H-isochromen-1-one → (3S)-6-(1-Hydroxy-2-(9-((R)-2-hydroxy-2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)ethyl)-3-oxa-7,9-diazabicyclo[3.3.1]nonan-7-yl)ethyl)-3-methylisochroman-1-one

HRID 2281348Notes

Reaction equation

HRID 2281348 reaction equation
[OH:1][C@H:2]([C:13]1[CH:22]=[CH:21][C:16]2[C:17](=[O:20])[O:18][CH2:19][C:15]=2[C:14]=1[CH3:23])[CH2:3][N:4]1[CH:9]2[CH2:10][NH:11][CH2:12][CH:5]1[CH2:6][O:7][CH2:8]2.[CH3:24][C@H:25]1[CH2:34][C:33]2[C:28](=[CH:29][CH:30]=[C:31]([CH:35]3[CH2:37][O:36]3)[CH:32]=2)[C:27](=[O:38])[O:26]1>>[OH:36][CH:35]([C:31]1[CH:32]=[C:33]2[C:28](=[CH:29][CH:30]=1)[C:27](=[O:38])[O:26][C@@H:25]([CH3:24])[CH2:34]2)[CH2:37][N:11]1[CH2:12][CH:5]2[N:4]([CH2:3][C@H:2]([OH:1])[C:13]3[C:14]([CH3:23])=[C:15]4[C:16](=[CH:21][CH:22]=3)[C:17](=[O:20])[O:18][CH2:19]4)[CH:9]([CH2:8][O:7][CH2:6]2)[CH2:10]1

Participants

3

Reactant 2

HCID 86693038(3S)-3-Methyl-6-(oxiran-2-yl)-3,4-dihydro-1H-isochromen-1-one2×HCID 1176420375-[(1R)-1-Hydroxy-2-(3-oxa-7,9-diazabicyclo[3.3.1]non-9-yl)ethyl]-4-methyl-2-benzofuran-1-(3H)-one2×

Product 1

HCID 71557352(3S)-6-(1-Hydroxy-2-(9-((R)-2-hydroxy-2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)ethyl)-3-oxa-7,9-diazabicyclo[3.3.1]nonan-7-yl)ethyl)-3-methylisochroman-1-one

Procedure

(3S)-6-(1-Hydroxy-2-(9-((R)-2-hydroxy-2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)ethyl)-3-oxa-7,9-diazabicyclo[3.3.1]nonan-7-yl)ethyl)-3-methylisochroman-1-one was prepared initially as a mixture of two diastereomers from 5-[(1R)-1-hydroxy-2-(3-oxa-7,9-diazabicyclo[3.3.1]non-9-yl)ethyl]-4-methyl-2-benzofuran-1(3H)-one [INTERMEDIATE 17] and (3S)-3-methyl-6-(oxiran-2-yl)-3,4-dihydro-1H-isochromen-1-one [INTERMEDIATE 24] in an analogous fashion to that described for the synthesis of EXAMPLE 1. The mixture of diastereomers was separated by preparative SFC-HPLC using a Chiralcel® OD column (30×250 mm) to afford the title single isomers.

Workup

  1. customthat described for the synthesis of EXAMPLE 1
  2. additionThe mixture of diastereomers
  3. customwas separated by preparative SFC-HPLC
  4. customto afford the title single isomers

Sources & evidence

ORD record
ord-5ad806281d074928a1b4516c1c988278
Source dataset
uspto-grants-2015_09
Patent number
US09139585B2

Reaction notes

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