Tetrahydrofuran → Tert-butyl (3-((5-(1-hydroxyethyl)-2-(methylthio)pyrimidin-4-yl)amino)phenyl)carbamate

HRID 527397Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 527397
[CH:1]([C:3]1[C:4]([NH:11][C:12]2[CH:13]=[C:14]([NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])[CH:15]=[CH:16][CH:17]=2)=[N:5][C:6]([S:9][CH3:10])=[N:7][CH:8]=1)=[O:2].[CH2:26]1COCC1.C[Mg]Br.[NH4+].[Cl-]>CCOCC>[OH:2][CH:1]([C:3]1[C:4]([NH:11][C:12]2[CH:13]=[C:14]([NH:18][C:19](=[O:25])[O:20][C:21]([CH3:22])([CH3:24])[CH3:23])[CH:15]=[CH:16][CH:17]=2)=[N:5][C:6]([S:9][CH3:10])=[N:7][CH:8]=1)[CH3:26]

Komponenten

6

Edukt 4

HCID 8028TetrahydrofuranHCID 25517Ammonium ChlorideHCID 57343702Tert-butyl (3-((5-formyl-2-(methylthio)pyrimidin-4-yl)amino)phenyl)carbamateHCID 178418573HCID 178418573, Verbindung

Produkt 1

HCID 86732008Tert-butyl (3-((5-(1-hydroxyethyl)-2-(methylthio)pyrimidin-4-yl)amino)phenyl)carbamateAusbeute 89 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 3283Diethyl EtherLösungsmittel

Reaktionsbedingungen

Temperatur
0.5 °C

Versuchsvorschrift

A 3-necked 2 L RBF equipped with an addition funnel, temperature probe and nitrogen inlet was charged with tert-butyl (3-((5-formyl-2-(methylthio)pyrimidin-4-yl)amino)phenyl)carbamate (50) (25.0 g, 69.4 mmol) and THF (400 mL). The mixture was cooled to 0.5° C. using an ice water bath. Methylmagnesium bromide (3.0 M in Et2O, 74.0 mL, 222 mmol) was added dropwise via an addition funnel over 35 min. The temperature was kept below 8° C. during the addition. The reaction mixture was stirred for 90 min at 0.5° C. and then saturated NH4Cl (aq.) was added slowly via an addition funnel while cooling in ice. The mixture was stirred for 1 h then extracted with EtOAc (2×300 mL). The combined organic layers were washed with brine, dried over anhydrous MgSO4, filtered and concentrated furnishing a yellow solid. The yellow solid was suspended in Et2O (ca. 200 mL), filtered, washed with additional Et2O (2×50 mL), and dried under vacuum overnight affording tert-butyl (3-((5-(1-hydroxyethyl)-2-(methylthio)pyrimidin-4-yl)amino)phenyl)carbamate (23.17 g, 61.5 mmol, 89% yield) as a light yellow solid. m/z (ESI, +ve ion) 377.0 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.34 (1H, s), 8.86 (1H, s), 8.07 (1H, s), 7.80 (1H, s), 7.32 (1H, dd, J=8.1, 1.1 Hz), 7.19 (1H, t, J=8.1 Hz), 6.95-7.07 (1H, m), 5.87 (1H, d, J=4.1 Hz), 4.93 (1H, dd, J=6.5, 4.3 Hz), 2.43 (3H, s), 1.47 (9H, s), 1.40 (3H, d, J=6.5 Hz).

Aufarbeitung

  1. customA 3-necked 2 L RBF equipped with an addition funnel
  2. additionThe temperature was kept below 8° C. during the addition
  3. temperaturewhile cooling in ice
  4. stirringThe mixture was stirred for 1 h
  5. extractionthen extracted with EtOAc (2×300 mL)
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over anhydrous MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customfurnishing a yellow solid
  11. filtrationfiltered
  12. washwashed with additional Et2O (2×50 mL)
  13. customdried under vacuum overnight

Quellen und Nachweise

ORD-Eintrag
ord-60e6e3bbedae4df5aee464fd418df9c6
Quelldatensatz
uspto-grants-2016_05
Patentnummer
US09346801B2

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