4-(4-methylpiperazin-1-yl)-4-oxobutanoic acid → HCID 178462422, compound

HRID 1766948Notes

Reaction equation

HRID 1766948 reaction equation
[C:1]([C:3]1[CH:4]=[CH:5][C:6]([CH2:49][OH:50])=[C:7]([CH:48]=1)[C:8]([O:10][C@:11]([C:40]1[CH:45]=[CH:44][C:43]([F:46])=[CH:42][C:41]=1[F:47])([CH2:34][N:35]1[CH:39]=[N:38][CH:37]=[N:36]1)[C@H:12]([S:14][C@@H:15]1[CH2:20][O:19][C@@H:18](/[CH:21]=[CH:22]/[CH:23]=[CH:24]/[C:25]2[CH:30]=[CH:29][C:28]([C:31]#[N:32])=[CH:27][C:26]=2[F:33])[O:17][CH2:16]1)[CH3:13])=[O:9])#[N:2].[CH3:51][N:52]1[CH2:57][CH2:56][N:55]([C:58](=[O:64])[CH2:59][CH2:60][C:61](O)=[O:62])[CH2:54][CH2:53]1.Cl.C(N=C=NCCCN(C)C)C>ClCCl.CN(C1C=CN=CC=1)C>[C:1]([C:3]1[CH:4]=[CH:5][C:6]([CH2:49][O:50][C:61](=[O:62])[CH2:60][CH2:59][C:58]([N:55]2[CH2:54][CH2:53][N:52]([CH3:51])[CH2:57][CH2:56]2)=[O:64])=[C:7]([CH:48]=1)[C:8]([O:10][C@:11]([C:40]1[CH:45]=[CH:44][C:43]([F:46])=[CH:42][C:41]=1[F:47])([CH2:34][N:35]1[CH:39]=[N:38][CH:37]=[N:36]1)[C@H:12]([S:14][C@@H:15]1[CH2:16][O:17][C@@H:18](/[CH:21]=[CH:22]/[CH:23]=[CH:24]/[C:25]2[CH:30]=[CH:29][C:28]([C:31]#[N:32])=[CH:27][C:26]=2[F:33])[O:19][CH2:20]1)[CH3:13])=[O:9])#[N:2]

Participants

6

Reactant 3

HCID 7393184-(4-methylpiperazin-1-yl)-4-oxobutanoic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 178462421HCID 178462421, compound

Product 1

HCID 178462422HCID 178462422, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalyst2×HCID 6344DichloromethaneSolvent2×

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 5-cyano-2-(hydroxymethyl)benzoate (1.38 g, 1.97 mmol) obtained from Example 33 in dichloromethane (40 ml) was cooled to 0° C., and 4-(N,N-dimethylamino)pyridine (481.3 mg, 3.94 mmol), 4-(4-methyl-1-piperazinyl)-4-oxobutanoic acid (described in Bioorg. Med. Chem., 8, 2693 (2000); 708.0 mg, 3.54 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (830.8 mg, 4.33 mmol) were added thereto. The reaction mixture was stirred at the same temperature for 2 hours, and diluted with dichloromethane, then the organic layer was washed successively with water and a saturated aqueous solution of sodium chloride. The solvent was evaporated under reduced pressure, and the obtained residue was subjected to chromatography on a silica gel (30 g) column (eluent; ethyl acetate:methanol=4:1) to afford a mixture of the title compound and 4-(N,N-dimethylamino)pyridine (component ratio; 6:1, 1.33 g). A part (790.8 mg) of the mixture was separated 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 (763.0 mg, 44% yield) as a colorless amorphous solid.

Workup

  1. washthe organic layer was washed successively with water
  2. customThe solvent was evaporated under reduced pressure
  3. customto afford

Sources & evidence

ORD record
ord-7c87fd78ba7446f69bf2d644791f97b9
Source dataset
uspto-grants-2007_06
Patent number
US07230023B2

Reaction notes

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