5-Chloro-N2-(2-fluoro-5-methyl-4-(1-methylpiperidin-4-yl)phenyl)-N4-(5-methyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamine → 5-chloro-N2-(2-fluoro-5-methyl-4-(piperidin-4-yl)phenyl)-N4-(5-methyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamine

HRID 536352Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 536352
[Cl:1][C:2]1[C:3]([NH:24][C:25]2[CH:29]=[C:28]([CH3:30])[NH:27][N:26]=2)=[N:4][C:5]([NH:8][C:9]2[CH:14]=[C:13]([CH3:15])[C:12]([CH:16]3[CH2:21][CH2:20][N:19](C)[CH2:18][CH2:17]3)=[CH:11][C:10]=2[F:23])=[N:6][CH:7]=1.NC1C(F)=CC(C2CCN(C(OC(C)(C)C)=O)CC2)=C(C)C=1>CC(O)C.Cl>[Cl:1][C:2]1[C:3]([NH:24][C:25]2[CH:29]=[C:28]([CH3:30])[NH:27][N:26]=2)=[N:4][C:5]([NH:8][C:9]2[CH:14]=[C:13]([CH3:15])[C:12]([CH:16]3[CH2:17][CH2:18][NH:19][CH2:20][CH2:21]3)=[CH:11][C:10]=2[F:23])=[N:6][CH:7]=1

Komponenten

5

Edukt 2

HCID 446126145-Chloro-N2-(2-fluoro-5-methyl-4-(1-methylpiperidin-4-yl)phenyl)-N4-(5-methyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamine2×HCID 58255168Tert-butyl 4-(4-amino-5-fluoro-2-methylphenyl)piperidine-1-carboxylate2×

Produkt 1

HCID 446126165-chloro-N2-(2-fluoro-5-methyl-4-(piperidin-4-yl)phenyl)-N4-(5-methyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamine

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 313Hydrochloric AcidKatalysatorHCID 3776IsopropanolLösungsmittel

Reaktionsbedingungen

Temperatur
130 °C

Versuchsvorschrift

A mixture of 2,5-dichloro-N-(5-methyl-1H-pyrazol-3-yl)pyrimidin-4-amine (Intermediate 1, 132 mg, 0.54 mmol) and tert-butyl 4-(4-amino-5-fluoro-2-methylphenyl)piperidine-1-carboxylate (Intermediate 19, 166 mg, 0.54 mmol) in 2-propanol (15 mL) was treated with conc. aqueous HCl (14 drops). The mixture was sealed and heated in a microwave at 130° C. for 60 min. The mixture was concentrated to afford 5-chloro-N2-(2-fluoro-5-methyl-4-(piperidin-4-yl)phenyl)-N4-(5-methyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamine as a yellow solid. A portion of the crude product was purified with preparative RP-HPLC to afford 5-chloro-N2-(2-fluoro-5-methyl-4-(piperidin-4-yl)phenyl)-N4-(5-methyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamine as a white solid; ESMS m/z 416.1 (M+H+). The remainder of the crude product was used directly for the next step without further purification.

Aufarbeitung

  1. customThe mixture was sealed
  2. concentrationThe mixture was concentrated

Quellen und Nachweise

ORD-Eintrag
ord-96e289cc64474b149f0c0ee4b00b229e
Quelldatensatz
uspto-grants-2014_10
Patentnummer
US08859574B2

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