4-Amino-3,5-dichlorobenzotrifluoride → 4-[[4-[2,6-Dichloro-4-(trifluoromethyl)anilino]pyrimidin-2-yl]amino]benzonitrile

HRID 1530877Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1530877
FC(F)(F)S(O[C:7]1[CH:12]=[CH:11][N:10]=[C:9]([NH:13][C:14]2[CH:19]=[CH:18][C:17]([C:20]#[N:21])=[CH:16][CH:15]=2)[N:8]=1)(=O)=O.[Cl:24][C:25]1[CH:30]=[C:29]([C:31]([F:34])([F:33])[F:32])[CH:28]=[C:27]([Cl:35])[C:26]=1[NH2:36]>O1CCOCC1>[Cl:24][C:25]1[CH:30]=[C:29]([C:31]([F:34])([F:32])[F:33])[CH:28]=[C:27]([Cl:35])[C:26]=1[NH:36][C:7]1[CH:12]=[CH:11][N:10]=[C:9]([NH:13][C:14]2[CH:15]=[CH:16][C:17]([C:20]#[N:21])=[CH:18][CH:19]=2)[N:8]=1

Komponenten

4

Edukt 2

HCID 1410944-Amino-3,5-dichlorobenzotrifluorideHCID 223984512-[(4-Cyanophenyl)amino]4-pyrimidinyl trifluoromethanesulfonate

Produkt 1

HCID 4887744-[[4-[2,6-Dichloro-4-(trifluoromethyl)anilino]pyrimidin-2-yl]amino]benzonitrileAusbeute 9,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
170 °C

Versuchsvorschrift

4-[[4-[(4-chloro-5-methyl-2-pyrimidinyl]amino]benzonitrile (0.01541 mol), 4-amino-3,5-dimethyl-benzonitrile (0.00219 mol), 1-methyl-2-pyrrolidinone (4 ml), 1,4-dioxane (15 ml) and diisopropylethylamine (0.0154 mol) were combined in a flask under a stream of argon and heated at 160-230° C. for 16 hours. CH2Cl2 and 1N NaOH were added, and the mixture was stirred 1 hour and filtered to give a brown solid (*). The CH2Cl2 filtrate was separated and was evaporated and purified by flash column chromatography (eluent: 2% CH3OH/CH2Cl2). The desired fractions were combined, evaporated and the residue was stirred in CH2Cl2. The solid precipitate was filtered off, combined with the brown solid (*) and recrystallized from CH3CN. The precipitate was filtered off and dried, yielding 1.57 g (29%) of 4-[[2-[(4-cyanophenyl)amino]-5-methyl-4-pyrimidinyl]amino]-3,5-dimethylbenzonitrile (compound 89). c) 2-[(4-cyanophenyl)amino]-4-pyrimidinyl trifluoromethanesulfonate (0.0022 mol) and 2,6-dichloro-4-(trifluoromethyl)-benzenamine (0.0044 mol) were combined in 1,4-dioxane (2.5 ml) and heated in a sealed tube under Ar at 170° C. for 40 hours. The reaction mixture was allowed to cool to room temperature. Silica gel was added, and the solvent was evaporated. The residue was purified by flash column chromatography over silica gel (eluent gradient: CH2Cl2:CH3OH:NH4OH 100:0:0 to 97:2.7:0.3). The desired fractions were collected and the solvent was evaporated. The residue was recrystallized from CH3CN, filtered off and dried, yielding 0.086 g (9.2%) of 4-[[4-[[2,6-dichloro-4-(trifluoromethyl)-phenyl]amino]-2-pyrimidinyl]amino]benzonitrile (compound 66).

Aufarbeitung

  1. temperatureto cool to room temperature
  2. additionSilica gel was added
  3. customthe solvent was evaporated
  4. customThe residue was purified by flash column chromatography over silica gel (eluent gradient: CH2Cl2:CH3OH:NH4OH 100:0:0 to 97:2.7:0.3)
  5. customThe desired fractions were collected
  6. customthe solvent was evaporated
  7. customThe residue was recrystallized from CH3CN
  8. filtrationfiltered off
  9. customdried

Quellen und Nachweise

ORD-Eintrag
ord-ca6142177ba846a8b6764443e5a648ec
Quelldatensatz
uspto-grants-2001_03
Patentnummer
US06197779B1

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