Diisopropylethylamine → 5-(3-Cyano-propyl)-1-(5-methyl-2-oxo-[1,3]dioxol-4-ylmethyl)-azepane-2-carboxylic acid [2-chloro-1-(3,4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide

HRID 901477Notes

Reaction equation

HRID 901477 reaction equation
N1C=CC=CC=C1.[Cl:8][CH:9]([CH3:37])[CH:10]([NH:22][C:23]([CH:25]1[CH2:31][CH2:30][CH:29]([CH2:32][CH2:33][CH2:34][C:35]#[N:36])[CH2:28][CH2:27][NH:26]1)=[O:24])[CH:11]1[CH:16]([OH:17])[CH:15]([OH:18])[CH:14]([OH:19])[CH:13]([S:20][CH3:21])[O:12]1.CCN(C(C)C)C(C)C.Br[CH2:48][C:49]1[O:50][C:51](=[O:55])[O:52][C:53]=1[CH3:54]>CN(C=O)C.CCOC(C)=O>[Cl:8][CH:9]([CH3:37])[CH:10]([NH:22][C:23]([CH:25]1[CH2:31][CH2:30][CH:29]([CH2:32][CH2:33][CH2:34][C:35]#[N:36])[CH2:28][CH2:27][N:26]1[CH2:48][C:49]1[O:50][C:51](=[O:55])[O:52][C:53]=1[CH3:54])=[O:24])[CH:11]1[CH:16]([OH:17])[CH:15]([OH:18])[CH:14]([OH:19])[CH:13]([S:20][CH3:21])[O:12]1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 64514761H-AzepineHCID 107741414-(Bromomethyl)-5-methyl-1,3-dioxol-2-oneHCID 115907815-(3-Cyano-propyl)-azepane-2-carboxylic acid [2-chloro-1-(3,4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide

Product 1

HCID 730272985-(3-Cyano-propyl)-1-(5-methyl-2-oxo-[1,3]dioxol-4-ylmethyl)-azepane-2-carboxylic acid [2-chloro-1-(3,4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of azepine compound prepared in example 7′ (5-(3-cyano-propyl)-azepane-2-carboxylic acid [2-chloro-1-(3,4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide, 100 mg) in DMF (2.0 mL) was added DIEA (181 μL) followed by 4-bromomethyl-5-methyl-[1,3]-dioxol-2-one (194 mg, prepared as described in J. Alexander, et al. J. Med. Chem, 1996, 39, 480-486). After stirring overnight EtOAc (30 mL) was added, the organic solution washed with brine (20 mL), dried over Na2SO4 and the solvents removed under reduced pressure. The resulting residue was purified by semi-preparative HPLC (Waters Nova-Pak® HR C18, 6 μm particle size, 60 Å pore size, 20 mm ID×100 mm) to provide the title compound (6 mg) of as a white solid.

Workup

  1. additionwas added
  2. washthe organic solution washed with brine (20 mL)
  3. dry with materialdried over Na2SO4
  4. customthe solvents removed under reduced pressure
  5. customThe resulting residue was purified by semi-preparative HPLC (Waters Nova-Pak® HR C18, 6 μm particle size, 60 Å pore size, 20 mm ID×100 mm)

Sources & evidence

ORD record
ord-d4792417be454acd9ca8c767f40be475
Source dataset
uspto-grants-2008_04
Patent number
US07361743B2

Reaction notes

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