Dimethylacetamide → 6-[(4-Hydroxybenzyl)amino]-2-methylpyrimidine-4-carbonitrile

HRID 1039048Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1039048
Cl[C:2]1[N:7]=[C:6]([CH3:8])[N:5]=[C:4]([NH:9][CH2:10][C:11]2[CH:16]=[CH:15][C:14]([O:17]C)=[CH:13][CH:12]=2)[CH:3]=1.C(P(C(C)(C)C)C1C=CC2C(=CC=CC=2)C=1C1C2C(=CC=CC=2)C=CC=1)(C)(C)C.C[C:49]([N:51](C)C)=O>FC(F)(F)C([O-])=O.[Pd+2].FC(F)(F)C([O-])=O.[Zn].[C-]#N.[Zn+2].[C-]#N>[OH:17][C:14]1[CH:15]=[CH:16][C:11]([CH2:10][NH:9][C:4]2[N:5]=[C:6]([CH3:8])[N:7]=[C:2]([C:49]#[N:51])[CH:3]=2)=[CH:12][CH:13]=1

Komponenten

7

Edukt 3

HCID 31374DimethylacetamideHCID 2734941(1,1'-Binaphthalen)-2-yldi-tert-butylphosphineHCID 624837716-chloro-N-(4-methoxybenzyl)-2-methylpyrimidin-4-amine

Produkt 1

HCID 669271566-[(4-Hydroxybenzyl)amino]-2-methylpyrimidine-4-carbonitrile

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 11186Zinc cyanide (Zn(CN)2)KatalysatorHCID 23994ZincKatalysatorHCID 2733347Palladium(II) trifluoroacetateKatalysator

Reaktionsbedingungen

Temperatur
95 °C

Versuchsvorschrift

6-chloro-N-(4-methoxybenzyl)-2-methylpyrimidin-4-amine (500 mg, 01.90 mmol) from Step 1 from this example, palladium (II) trifluoroacetate (27.1 mg, 0.082 mmol), zinc dust (23.6 mg, 0.36 mmol), rac-2-(di-t-butylphosphino)-1,1-binaphthyl (66.5 mg, 0.17 mmol), zinc cyanide (125 mg, 1.1 mmol) was added dimethylacetamide (10 mL) in a flask (flame-dried) and evacuated and back-filled with N2 (3×). The reaction was heated to 95° C. for 30 min, cooled to room temperature. Water (20 mL) was added, extracted with ethyl acetate (20 mL), second wash with brine (20 mL). The organic phase was dried by magnesium sulfate and filtered through silica gel pad (1 inch deep), concentrated and purified by column chromatography through a 40 gram RediSep Rf™ silica gel cartridge eluting with 18% ethyl acetate/hexanes to give the title compounds as a pale yellow oil.

Aufarbeitung

  1. custom(flame-dried)
  2. customevacuated
  3. additionback-filled with N2 (3×)
  4. temperaturecooled to room temperature
  5. additionWater (20 mL) was added
  6. extractionextracted with ethyl acetate (20 mL)
  7. washsecond wash with brine (20 mL)
  8. dry with materialThe organic phase was dried by magnesium sulfate
  9. filtrationfiltered through silica gel pad (1 inch deep)
  10. concentrationconcentrated
  11. custompurified by column chromatography through a 40 gram RediSep Rf™ silica gel cartridge
  12. washeluting with 18% ethyl acetate/hexanes

Quellen und Nachweise

ORD-Eintrag
ord-974287041ca54e3e8b26127abe3ea4a3
Quelldatensatz
uspto-grants-2013_10
Patentnummer
US08552022B2

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