p-Toluenesulfonic acid → 2-(4-((4-((4-cyano-2,6-difluorobenzyl)amino)pyrimidin-2-yl)amino)-1H-pyrazol-1-yl)-N-isopropylacetamide

HRID 929909Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 929909
Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([NH:8][C:9]2[CH:10]=[N:11][N:12]([CH2:14][C:15]([NH:17][CH:18]([CH3:20])[CH3:19])=[O:16])[CH:13]=2)[N:3]=1.[NH2:21][CH2:22][C:23]1[C:30]([F:31])=[CH:29][C:26]([C:27]#[N:28])=[CH:25][C:24]=1[F:32].CC1C=CC(S(O)(=O)=O)=CC=1>O1CCOCC1>[C:27]([C:26]1[CH:25]=[C:24]([F:32])[C:23]([CH2:22][NH:21][C:2]2[CH:7]=[CH:6][N:5]=[C:4]([NH:8][C:9]3[CH:10]=[N:11][N:12]([CH2:14][C:15]([NH:17][CH:18]([CH3:20])[CH3:19])=[O:16])[CH:13]=3)[N:3]=2)=[C:30]([F:31])[CH:29]=1)#[N:28]

Komponenten

5

Edukt 3

HCID 6101p-Toluenesulfonic acidHCID 219055604-(Aminomethyl)-3,5-difluorobenzonitrileHCID 900240272-(4-(4-chloropyrimidin-2-ylamino)-1H-pyrazol-1-yl)-N-isopropylacetamide

Produkt 1

HCID 727064692-(4-((4-((4-cyano-2,6-difluorobenzyl)amino)pyrimidin-2-yl)amino)-1H-pyrazol-1-yl)-N-isopropylacetamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

A solution of 2-(4-(4-chloropyrimidin-2-ylamino)-1H-pyrazol-1-yl)-N-isopropylacetamide (120 mg, 0.41 mmol) (II-1, prepared by Procedure D), 4-(aminomethyl)-3,5-difluorobenzonitrile (68 mg, 0.41 mmol) (III-1, prepared by Procedure E) and TsOH (56 mg, 0.33 mmol) in dioxane (2 mL) was heated to 160° C. for 2 h then concentrated in vacuo. The residue was dissolved in ethyl acetate, washed with Na2CO3(aq), dried (Na2SO4), concentrated in vacuo and purified by prep. TLC (5-10% v/v MeOH/DCM) to afford 2-(4-((4-((4-cyano-2,6-difluorobenzyl)amino)pyrimidin-2-yl)amino)-1H-pyrazol-1-yl)-N-isopropylacetamide I-1 (50 mg, 29%) as a white solid. LC-MS (Method A), RT=8.02 min. (ES+) 427.

Aufarbeitung

  1. concentrationthen concentrated in vacuo
  2. dissolutionThe residue was dissolved in ethyl acetate
  3. washwashed with Na2CO3(aq)
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated in vacuo
  6. custompurified by prep

Quellen und Nachweise

ORD-Eintrag
ord-a6ef61f3edfd4753a41c7eadd4cdf7cc
Quelldatensatz
uspto-grants-2016_03
Patentnummer
US09296725B2

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