Sodium hydride → Methyl (2E)-4-{[4-(4-cyanophenyl)-1,3-thiazol-2-yl]amino}-4-methylpent-2-enoate

HRID 1436430Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1436430
[H-].[Na+].[CH3:3][O:4][C:5]([CH2:7]P(OC)(OC)=O)=[O:6].[CH3:14][C:15]([NH:19][C:20]1[S:21][CH:22]=[C:23]([C:25]2[CH:32]=[CH:31][C:28]([C:29]#[N:30])=[CH:27][CH:26]=2)[N:24]=1)([CH3:18])[CH:16]=O>O1CCCC1>[C:29]([C:28]1[CH:27]=[CH:26][C:25]([C:23]2[N:24]=[C:20]([NH:19][C:15]([CH3:18])([CH3:16])/[CH:14]=[CH:7]/[C:5]([O:4][CH3:3])=[O:6])[S:21][CH:22]=2)=[CH:32][CH:31]=1)#[N:30]

Komponenten

5

Edukt 3

HCID 24758Sodium hydrideHCID 80029Trimethyl phosphonoacetateHCID 866186094-{2-[(1,1-Dimethyl-2-oxoethyl)amino]-1,3-thiazol-4-yl}benzonitrile

Produkt 1

HCID 86618612Methyl (2E)-4-{[4-(4-cyanophenyl)-1,3-thiazol-2-yl]amino}-4-methylpent-2-enoateAusbeute 93 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

To a suspension of sodium hydride (60% in oil, 0.17 g, 4.5 mmol) in tetrahydrofuran (30 mL) was added trimethyl phosphonoacetate (0.75 mL, 5.2 mmol) dropwise and the mixture was stirred for 45 min. A solution of 4-{2-[(1,1-dimethyl-2-oxoethyl)amino]-1,3-thiazol-4-yl}benzonitrile (0.81 g, 3.0 mmol), prepared in step 1 of Example 83, in 5 mL of tetrahydrofuran was added and the mixture was stirred at 25° C. for 2 h. The reaction was quenched with saturated NH4Cl and diluted with ethyl acetate and washed with H2O, brine, dried over anhydrous MgSO4, filtered and concentrated. Flash chromatography (20% acetone/hexane) afforded methyl (2E)-4-{[4-(4-cyanophenyl)-1,3-thiazol-2-yl]amino}-4-methylpent-2-enoate (0.91 g, 93%) as a white solid. HRMS: calcd for C17H17N3O2S+H+, 328.11142; found (ESI, [M+H]+), 328.1135; Analytical HPLC: purity 100% at 210-370 nm, 9.9 min; 100% at 252 nm, 9.9 min; the Xterra® RP18 column, 3.5μ, 150×4.6 mm column, 1.2 mL/min, 85/15-5/95 (Ammon. Form. Buff. pH=3.5/ACN+MeOH) for 10 min, hold 4 min.

Aufarbeitung

  1. additionwas added
  2. stirringthe mixture was stirred at 25° C. for 2 h
  3. customThe reaction was quenched with saturated NH4Cl
  4. additiondiluted with ethyl acetate
  5. washwashed with H2O, brine
  6. dry with materialdried over anhydrous MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-93e9fec51a464378b144764fd9ee8bf8
Quelldatensatz
uspto-grants-2009_11
Patentnummer
US07618990B2

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