Sodium hydride → HCID 178459564, compound

HRID 1766895Notes

Reaction equation

HRID 1766895 reaction equation
[C:1]([O:14][CH2:15][CH:16]=[CH2:17])(=[O:13])[CH2:2][CH2:3][C:4]([O:6][CH2:7][CH2:8][CH2:9][C:10](Cl)=[O:11])=[O:5].[F:18][C:19]1[CH:24]=[C:23]([F:25])[CH:22]=[CH:21][C:20]=1[C@@:26]([OH:55])([CH2:49][N:50]1[CH:54]=[N:53][CH:52]=[N:51]1)[C@H:27]([S:29][C@@H:30]1[CH2:35][O:34][C@@H:33](/[CH:36]=[CH:37]/[CH:38]=[CH:39]/[C:40]2[CH:47]=[CH:46][C:43]([C:44]#[N:45])=[CH:42][C:41]=2[F:48])[O:32][CH2:31]1)[CH3:28].[H-].[Na+]>>[C:1]([O:14][CH2:15][CH:16]=[CH2:17])(=[O:13])[CH2:2][CH2:3][C:4]([O:6][CH2:7][CH2:8][CH2:9][C:10]([O:55][C@:26]([C:20]1[CH:21]=[CH:22][C:23]([F:25])=[CH:24][C:19]=1[F:18])([CH2:49][N:50]1[CH:54]=[N:53][CH:52]=[N:51]1)[C@H:27]([S:29][C@@H:30]1[CH2:31][O:32][C@@H:33](/[CH:36]=[CH:37]/[CH:38]=[CH:39]/[C:40]2[CH:47]=[CH:46][C:43]([C:44]#[N:45])=[CH:42][C:41]=2[F:48])[O:34][CH2:35]1)[CH3:28])=[O:11])=[O:5]

Participants

4

Reactant 3

HCID 24758Sodium hydrideHCID 86594587Allyl 4-chloro-4-oxobutyl succinateHCID 178462432HCID 178462432, compound

Product 1

HCID 178459564HCID 178459564, compoundYield 40%

Procedure

The crude allyl 4-chloro-4-oxobutyl succinate was treated with 4-[(1E,3E)-4-[trans-5-[[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]thio]-1,3-dioxan-2-yl]-1,3-butadienyl]-3-fluorobenzonitrile (814 mg, 1.50 mmol) described in Reference example 1 and sodium hydride (55% dispersion in mineral oil; 70 mg, 1.6 mmol) according to a similar procedure to that described in Example 13-(2). The obtained crude title compound was purified by recycle preparative HPLC [LC-908; Japan Analytical Industry Co., Ltd.; GPC column JAIGEL-1H (20 mm i.d.×600 mm) and JAIGEL-2H (20 mm i.d.×600 mm) connected in series for use; solvent, chloroform] to afford the title compound (459 mg, 40% yield) as a colorless viscous material.

Workup

  1. customThe obtained crude title compound
  2. customwas purified by recycle preparative HPLC [LC-908; Japan Analytical Industry Co., Ltd.; GPC column JAIGEL-1H (20 mm i.d.×600 mm) and JAIGEL-2H (20 mm i.d.×600 mm) connected in series for use; solvent, chloroform]

Sources & evidence

ORD record
ord-bc896941e1914bc9966d4bb03e7027dd
Source dataset
uspto-grants-2007_06
Patent number
US07230023B2

Reaction notes

Loading…