Toluene → N-[4-Methyl-3-(3-methyl-3-{6-[4-(4-methyl-piperazin-1-yl)-phenyl-amino]-pyrimidin-4-yl}-ureido)-phenyl]-3-trifluoromethyl-benzamide

HRID 1038730Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1038730
[NH2:1][C:2]1[CH:3]=[C:4]([NH:9][C:10](=[O:21])[C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([C:17]([F:20])([F:19])[F:18])[CH:12]=2)[CH:5]=[CH:6][C:7]=1[CH3:8].[C:22](Cl)(Cl)=[O:23].C1(C)C=CC=CC=1.[CH3:33][NH:34][C:35]1[CH:40]=[C:39]([NH:41][C:42]2[CH:47]=[CH:46][C:45]([N:48]3[CH2:53][CH2:52][N:51]([CH3:54])[CH2:50][CH2:49]3)=[CH:44][CH:43]=2)[N:38]=[CH:37][N:36]=1>O1CCOCC1.CCOCC>[CH3:8][C:7]1[CH:6]=[CH:5][C:4]([NH:9][C:10](=[O:21])[C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([C:17]([F:18])([F:19])[F:20])[CH:12]=2)=[CH:3][C:2]=1[NH:1][C:22]([N:34]([CH3:33])[C:35]1[CH:40]=[C:39]([NH:41][C:42]2[CH:47]=[CH:46][C:45]([N:48]3[CH2:53][CH2:52][N:51]([CH3:54])[CH2:50][CH2:49]3)=[CH:44][CH:43]=2)[N:38]=[CH:37][N:36]=1)=[O:23]

Komponenten

7

Edukt 4

HCID 1140TolueneHCID 6371PhosgeneHCID 11529455N-(3-amino-4-methylphenyl)-3-(trifluoromethyl)benzamideHCID 66669969N-methyl-N'-[4-(4-methyl-piperazin-1-yl)-phenyl]-pyrimidine-4,6-diamine

Produkt 1

HCID 11592548N-[4-Methyl-3-(3-methyl-3-{6-[4-(4-methyl-piperazin-1-yl)-phenyl-amino]-pyrimidin-4-yl}-ureido)-phenyl]-3-trifluoromethyl-benzamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 3283Diethyl EtherLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

To a solution of N-(3-Amino-4-methyl-phenyl)-3-trifluoromethyl-benzamide (preparation 3, 62 mg, 0.21 mmol, 1.25 eq.) in dioxane is added 20% phosgene solution in toluene (110 μl, 0.21 mmol, 1.25 eq.) under argon. The reaction mixture is stirred for further 22 h at room temperature under argon. Then, the solvent is evaporated and the residue is taken up in dry toluene (2 ml). After the addition of N-Methyl-N′-[4-(4-methyl-piperazin-1-yl)-phenyl]-pyrimidine-4,6-diamine (50 mg, 0.168 mmol, 1.0 eq.) the suspension is refluxed for 24 h under argon. After cooling ether (2 ml) is added and the mixture is stirred for 30 min. The precipitated product is filtered off, washed (1× toluene/ether 1:1, 1× ether) and vacuum dried at 60° C. overnight to afford the title compound as colorless crystals: M.p. 189.5-191° C., HPLC: tR=6.02 min (purity: >99%, gradient A), ESI-MS: 619.6 [MH]+.

Aufarbeitung

  1. customThen, the solvent is evaporated
  2. temperatureis refluxed for 24 h under argon
  3. additionis added
  4. stirringthe mixture is stirred for 30 min
  5. filtrationThe precipitated product is filtered off
  6. washwashed (1× toluene/ether 1:1, 1× ether) and vacuum
  7. customdried at 60° C. overnight

Quellen und Nachweise

ORD-Eintrag
ord-1edff73dbcf04ddb88d73a53fa2dc281
Quelldatensatz
uspto-grants-2013_10
Patentnummer
US08552002B2

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