Dimethylformamide → 4-chloro-N-(2-chloro-3-fluoro-phenyl)-N-methyl-3-(6-methyl-2-oxo-4-trifluoromethyl-2H-pyrimidin-1-yl)-benzamide

HRID 661668

Reaktionsgleichung

Reaktionsgleichung von HRID 661668
[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][C:3]=1[N:11]1[C:16]([CH3:17])=[CH:15][C:14]([C:18]([F:21])([F:20])[F:19])=[N:13][C:12]1=[O:22].C(Cl)(=O)C(Cl)=O.CN(C=O)C.[CH3:34][NH:35][C:36]1[CH:41]=[CH:40][CH:39]=[C:38]([F:42])[C:37]=1[Cl:43]>ClCCCl.CN(C)C1C=CN=CC=1>[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([N:35]([C:36]2[CH:41]=[CH:40][CH:39]=[C:38]([F:42])[C:37]=2[Cl:43])[CH3:34])=[O:8])=[CH:4][C:3]=1[N:11]1[C:16]([CH3:17])=[CH:15][C:14]([C:18]([F:21])([F:20])[F:19])=[N:13][C:12]1=[O:22]

Komponenten

7

Edukt 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 552789582-chloro-3-fluoro-N-methylanilineHCID 686037674-chloro-3-(6-methyl-2-oxo-4-trifluoromethyl-2H-pyrimidin-1-yl)-benzoic acid

Produkt 1

HCID 593703364-chloro-N-(2-chloro-3-fluoro-phenyl)-N-methyl-3-(6-methyl-2-oxo-4-trifluoromethyl-2H-pyrimidin-1-yl)-benzamideAusbeute 25,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 111,2-DichloroethaneLösungsmittel2×

Versuchsvorschrift

To a stirred solution of 4-chloro-3-(6-methyl-2-oxo-4-trifluoromethyl-2H-pyrimidin-1-yl)-benzoic acid (50 mg, 0.151 mmol) in anhydrous 1,2-dichloroethane (0.5 mL) at room temperature was added oxalyl chloride (23 mg, 0.181 mmol) followed by a catalytic amount of DMF. After stirring for 40 mins, a solution of N-methyl-2-chloro-3-fluoroaniline 29-1 (30 mg, 0.188 mmol) in 1,2-dichloroethane (0.5 mL), followed by 4-(dimethylamino)pyridine (22 mg, 0.179 mmol) were added and the mixture was stirred for 12 h. Direct purification via reverse phase preparative LCMS gave 4-chloro-N-(2-chloro-3-fluoro-phenyl)-N-methyl-3-(6-methyl-2-oxo-4-trifluoromethyl-2H-pyrimidin-1-yl)-benzamide 30-1 (18 mg, 25%) as a colorless solid. MS: 350.5, tR=8.75 min (method 3); 1H NMR (CDCl3) δ 7.50 (1H, m), 7.44 (1H, dd, J=8.4, 1.8 Hz), 7.31 (1H, m), 7.26 (1H, s), 6.95 (1H, dd, J=9, 2.1 Hz), 6.79 (1H, m), 6.55 (1H, s), 3.46 (3H, s), 1.93 (3H, s).

Aufarbeitung

  1. additionwere added
  2. stirringthe mixture was stirred for 12 h
  3. customDirect purification via reverse phase preparative LCMS

Quellen und Nachweise

ORD-Eintrag
ord-1ee025daff0f4eec8578fcd6da053c0d
Quelldatensatz
uspto-grants-2011_12
Patentnummer
US08084614B2

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