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Potassium Fluoride → Tert-butyl[5-(3-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]carbamate

HRID 1028092
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Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1028092
C(P(C12CC3CC(CC(C3)C1)C2)C12CC3CC(CC(C3)C1)C2)CCC.CC1(C)C(C)(C)OB([C:34]2[CH:35]=[C:36]([NH:40][C:41]3[N:46]=[C:45]([C:47]([F:50])([F:49])[F:48])[CH:44]=[CH:43][N:42]=3)[CH:37]=[CH:38][CH:39]=2)O1.Br[C:53]1[S:57][C:56]([NH:58][C:59](=[O:65])[O:60][C:61]([CH3:64])([CH3:63])[CH3:62])=[N:55][CH:54]=1.[F-].[K+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.C1COCC1>[C:61]([O:60][C:59](=[O:65])[NH:58][C:56]1[S:57][C:53]([C:34]2[CH:39]=[CH:38][CH:37]=[C:36]([NH:40][C:41]3[N:46]=[C:45]([C:47]([F:48])([F:49])[F:50])[CH:44]=[CH:43][N:42]=3)[CH:35]=2)=[CH:54][N:55]=1)([CH3:64])([CH3:62])[CH3:63]
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Komponenten

8

Edukt 4

HCID 522689Potassium FluorideHCID 11371790Bis(adamantan-1-yl)(butyl)phosphaneHCID 21300388tert-butyl N-(5-bromo-1,3-thiazol-2-yl)carbamateHCID 58456307N-(3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-4-(trifluoromethyl)pyrimidin-2-amine2×

Produkt 1

HCID 86674323
Tert-butyl[5-(3-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]carbamate
Ausbeute 27,2 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 167845palladium(II) acetateKatalysatorHCID 962WaterLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

A sealable reaction tube was charged with, palladium (II) acetate (6.15 mg, 0.027 mmol), butyldi-1-adamantylphosphine (19.64 mg, 0.055 mmol) and THF (4 mL) and was stirred for 10 minutes under nitrogen. N-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine (200 mg, 0.548 mmol) (Intermediate VII), tert-butyl (5-bromo-1,3-thiazol-2-yl)carbamate (199 mg, 0.712 mmol), potassium fluoride (95 mg, 1.643 mmol) and Water (1.333 mL) were then successively added. The tube was capped and the mixture was stirred at 75° C. for 17 hours, cooled to room temperature and quenched by the addition of 25% aqueous NH4OAc. The aqueous layer was extracted twice with ethyl acetate. The combined organic fractions were washed with water and brine, dried over Na2SO4 and concentrated. The product was purified by column chromatography on silica gel (ethyl acetate/hexane) to afford tert-butyl[5-(3-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]carbamate (65.1 mg, 27.2%) as a beige solid. APCI [M+H]+ m/z 382 Step 2:

Aufarbeitung

  1. customThe tube was capped
  2. stirringthe mixture was stirred at 75° C. for 17 hours
  3. customquenched by the addition of 25% aqueous NH4OAc
  4. extractionThe aqueous layer was extracted twice with ethyl acetate
  5. washThe combined organic fractions were washed with water and brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. customThe product was purified by column chromatography on silica gel (ethyl acetate/hexane)

Quellen und Nachweise

ORD-Eintrag
ord-a405c7a0f892467caa5a9f89a3328a27
Quelldatensatz
uspto-grants-2014_05
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08735417B2

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