Hydrochloric Acid → 3-(((1R,2R)-2-amino-3,3-difluorocyclohexyl)amino)-5-((3-(pyrimidin-2-yl)phenyl)amino)-1,2,4-triazine-6-carboxamide

HRID 577420Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 577420
CS[C:3]1[N:4]=[N:5][C:6]([C:22]([NH2:24])=[O:23])=[C:7]([NH:9][C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([C:16]3[N:21]=[CH:20][CH:19]=[CH:18][N:17]=3)[CH:11]=2)[N:8]=1.C1C=C(Cl)C=C(C(OO)=O)C=1.CCN(C(C)C)C(C)C.Cl.Cl.[F:47][C:48]1([F:56])[CH2:53][CH2:52][CH2:51][C@@H:50]([NH2:54])[C@H:49]1[NH2:55].C(O)(C(F)(F)F)=O.Cl>CN1C(=O)CCC1>[NH2:55][C@H:49]1[C:48]([F:56])([F:47])[CH2:53][CH2:52][CH2:51][C@H:50]1[NH:54][C:3]1[N:4]=[N:5][C:6]([C:22]([NH2:24])=[O:23])=[C:7]([NH:9][C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([C:16]3[N:21]=[CH:20][CH:19]=[CH:18][N:17]=3)[CH:11]=2)[N:8]=1

Komponenten

8

Edukt 6

HCID 313Hydrochloric AcidHCID 6422Trifluoroacetic acidHCID 70297m-Chloroperbenzoic acidHCID 81531DiisopropylethylamineHCID 86685557(1R,2R)-3,3-difluorocyclohexane-1,2-diamine dihydrochlorideHCID 867064133-(Methylthio)-5-(3-(pyrimidin-2-yl)phenylamino)-1,2,4-triazine-6-carboxamide

Produkt 1

HCID 727032273-(((1R,2R)-2-amino-3,3-difluorocyclohexyl)amino)-5-((3-(pyrimidin-2-yl)phenyl)amino)-1,2,4-triazine-6-carboxamideAusbeute 66,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 13387N-methyl-2-pyrrolidoneLösungsmittel

Versuchsvorschrift

3-(Methylthio)-5-(3-(pyrimidin-2-yl)phenylamino)-1,2,4-triazine-6-carboxamide (40 mg, 0.12 mmol) was dissolved in 4 mL NMP. To it was added mCPBA (77%) (108 mg, 0.48 mmol). The mixture was stirred at RT for 1 h. To it was added DIEA (0.21 mL, 1.20 mmol) and (1R,2R)-3,3-difluorocyclohexane-1,2-diamine dihydrochloride (53 mg, 0.24 mmol). The mixture was stirred at 80° C. for 1 h. It was cooled to RT, acidified with TFA (0.3 mL) and subjected to reverse phase preparative HPLC to isolate the title compound (35 mg) as HCl salt. MS found for C20H21F2N9O as (M+H)+ 442.5. UV: λ=240 nm. Proton NMR: (CD3OD) δ 8.94-8.92 (3H, m), 8.41 (1H, d, J=8.0 Hz), 7.79 (1H, d, J=8.0 Hz), 7.64 (1H, t, J=8.0 Hz), 7.45 (1H, t, J=4.8 Hz), 4.90 (1H, m), 4.13 (1H, m), 2.24-1.82 (6H, m) ppm.

Aufarbeitung

  1. stirringThe mixture was stirred at 80° C. for 1 h
  2. temperatureIt was cooled to RT

Quellen und Nachweise

ORD-Eintrag
ord-401d987570874833b73dd58a3b875d23
Quelldatensatz
uspto-grants-2015_05
Patentnummer
US09040530B2

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