N,N-Dimethylglycine → HCID 178462420, compound

HRID 1766934Notes

Reaction equation

HRID 1766934 reaction equation
[OH:1][CH2:2][C:3]1[CH:48]=[CH:47][CH:46]=[CH:45][C:4]=1[C:5]([O:7][C@:8]([C:37]1[CH:42]=[CH:41][C:40]([F:43])=[CH:39][C:38]=1[F:44])([CH2:31][N:32]1[CH:36]=[N:35][CH:34]=[N:33]1)[C@H:9]([S:11][C@@H:12]1[CH2:17][O:16][C@@H:15](/[CH:18]=[CH:19]/[CH:20]=[CH:21]/[C:22]2[CH:27]=[CH:26][C:25]([C:28]#[N:29])=[CH:24][C:23]=2[F:30])[O:14][CH2:13]1)[CH3:10])=[O:6].[CH3:49][N:50]([CH3:55])[CH2:51][C:52](O)=[O:53].[Cl-].ClC1N(C)CC[NH+]1C.CN1CCN(C)C1=O>ClCCl.CN(C1C=CN=CC=1)C.C(OCC)(=O)C>[CH3:49][N:50]([CH2:51][C:52]([O:1][CH2:2][C:3]1[CH:48]=[CH:47][CH:46]=[CH:45][C:4]=1[C:5]([O:7][C@:8]([C:37]1[CH:42]=[CH:41][C:40]([F:43])=[CH:39][C:38]=1[F:44])([CH2:31][N:32]1[CH:36]=[N:35][CH:34]=[N:33]1)[C@H:9]([S:11][C@@H:12]1[CH2:17][O:16][C@@H:15](/[CH:18]=[CH:19]/[CH:20]=[CH:21]/[C:22]2[CH:27]=[CH:26][C:25]([C:28]#[N:29])=[CH:24][C:23]=2[F:30])[O:14][CH2:13]1)[CH3:10])=[O:6])=[O:53])[CH3:55]

Participants

8

Reactant 4

HCID 673N,N-DimethylglycineHCID 66611,3-Dimethyl-2-imidazolidinoneHCID 109867151H-Imidazolium, 2-chloro-4,5-dihydro-1,3-dimethyl-, chlorideHCID 178462418HCID 178462418, compound

Product 1

HCID 178462420HCID 178462420, compound

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of (1R,2R)-2-[[trans-2-[(1E,3E)-4-(4-cyano-2-fluorophenyl)-1,3-butadienyl]-1,3-dioxan-5-yl]thio]-1-(2,4-difluorophenyl)-1-[(1H-1,2,4-triazol-1-yl)methyl]propyl 2-(hydroxymethyl)benzoate (640.7 mg, 0.95 mmol) obtained from Example 17-(4) in dichloromethane (20 ml) was cooled to 0° C., and then 4-(N,N-dimethylamino)pyridine (254.5 mg, 2.1 mmol), N,N-dimethylglycine (117.2 mg, 1.14 mmol), and 2-chloro-1,3-dimethylimidazolinium chloride (256.1 mg, 1.52 mmol) were added thereto. The reaction mixture was stirred at room temperature for 3 hours, diluted with ethyl acetate, and then the organic layer was washed successively with a saturated aqueous solution of ammonium chloride and with a saturated aqueous solution of sodium chloride. The solvent was evaporated under reduced pressure, and then the residue was subjected to chromatography on a silica gel (40 g) column (eluent; ethyl acetate:methanol=100:3) to give a mixture of the title compound and 1,3-dimethyl-2-imidazolidinone. The mixture 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 target compound (368.1 mg, 51% yield) as a colorless amorphous solid.

Workup

  1. washthe organic layer was washed successively with a saturated aqueous solution of ammonium chloride and with a saturated aqueous solution of sodium chloride
  2. customThe solvent was evaporated under reduced pressure
  3. customto give

Sources & evidence

ORD record
ord-30fd0686ebcb48728792afea273d044c
Source dataset
uspto-grants-2007_06
Patent number
US07230023B2

Reaction notes

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