5-(Trifluoromethyl)pyrimidin-2-amine → (S)-2-[4-(5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl]-morpholine-4-carboxylic acid tert-butyl ester

HRID 2403279Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2403279
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][O:11][C@@H:10]([C:14]2[CH:19]=[CH:18][C:17](Br)=[CH:16][CH:15]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:21][C:22]([F:31])([F:30])[C:23]1[CH:24]=[N:25][C:26]([NH2:29])=[N:27][CH:28]=1>O1CCOCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][O:11][C@@H:10]([C:14]2[CH:19]=[CH:18][C:17]([NH:29][C:26]3[N:25]=[CH:24][C:23]([C:22]([F:31])([F:21])[F:30])=[CH:28][N:27]=3)=[CH:16][CH:15]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Komponenten

4

Edukt 2

HCID 152735745-(Trifluoromethyl)pyrimidin-2-amineHCID 58097875tert-butyl (2S)-2-(4-bromophenyl)morpholine-4-carboxylate

Produkt 1

HCID 68325411(S)-2-[4-(5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl]-morpholine-4-carboxylic acid tert-butyl esterAusbeute 108,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

To a 10 ml glass vial was added (S)-2-(4-bromo-phenyl)-morpholine-4-carboxylic acid tert-butyl ester (70 mg, CAS 1131220-37-5) and 5-trifluoromethyl-pyrimidin-2-ylamine (66.7 mg, CAS 69034-08-8) in dioxane (2 ml). The reaction mixture was purged with argon for 5 min. 2-Di-tert-butylphosphino-2′,4′,6′-triisopropylbiphenyl (14.3 mg), tris(dibenzylideneacetone)dipalladium(0) (7.49 mg) and sodium tert-butoxide (21.6 mg) were then added. The vial was capped and heated at 120° C. for 16 h. The reaction mixture was then filtered through sintered glass and the filtrate was concentrated in vacuo. The residue was purified by flash column chromatography (silica gel; gradient: 0% to 50% EtOAc in hexanes) to afford (S)-2-[4-(5-trifluoromethyl-pyrimidin-2-ylamino)-phenyl]-morpholine-4-carboxylic acid tert-butyl ester (94 mg, quant.) as an off-white solid. MS (ISP): 425.2 ([M+H]+).

Aufarbeitung

  1. customThe reaction mixture was purged with argon for 5 min
  2. addition2-Di-tert-butylphosphino-2′,4′,6′-triisopropylbiphenyl (14.3 mg), tris(dibenzylideneacetone)dipalladium(0) (7.49 mg) and sodium tert-butoxide (21.6 mg) were then added
  3. customThe vial was capped
  4. filtrationThe reaction mixture was then filtered through sintered glass
  5. concentrationthe filtrate was concentrated in vacuo
  6. customThe residue was purified by flash column chromatography (silica gel; gradient: 0% to 50% EtOAc in hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-14c4d712d9e343f581bd3591cd96bc1f
Quelldatensatz
uspto-grants-2014_08
Patentnummer
US08802673B2

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