Acetic Anhydride → (S)-2-(4-(3-(tert-butoxy)-2-(4-(tert-butyl)benzamido)-3-oxopropyl)phenyl)pyrimidine-5-carboxylic acid

HRID 1775861Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1775861
[CH:1]([O-:3])=[O:2].[Li+].CCN(C(C)C)C(C)C.C(OC(=O)C)(=O)C.Br[C:22]1[CH:23]=[N:24][C:25]([C:28]2[CH:33]=[CH:32][C:31]([CH2:34][C@H:35]([NH:43][C:44](=[O:55])[C:45]3[CH:50]=[CH:49][C:48]([C:51]([CH3:54])([CH3:53])[CH3:52])=[CH:47][CH:46]=3)[C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])=[CH:30][CH:29]=2)=[N:26][CH:27]=1>CN(C=O)C.C(O)(=O)CC(CC(O)=O)(C(O)=O)O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:39]([O:38][C:36](=[O:37])[C@@H:35]([NH:43][C:44](=[O:55])[C:45]1[CH:50]=[CH:49][C:48]([C:51]([CH3:54])([CH3:53])[CH3:52])=[CH:47][CH:46]=1)[CH2:34][C:31]1[CH:32]=[CH:33][C:28]([C:25]2[N:24]=[CH:23][C:22]([C:1]([OH:3])=[O:2])=[CH:27][N:26]=2)=[CH:29][CH:30]=1)([CH3:42])([CH3:41])[CH3:40]

Komponenten

8

Edukt 4

HCID 7918Acetic AnhydrideHCID 81531DiisopropylethylamineHCID 23680280Lithium formateHCID 86689676tert-butyl (S)-3-(4-(5-bromopyrimidin-2-yl)phenyl)-2-(4-(tert-butyl)benzamido)propanoate

Produkt 1

HCID 117740712(S)-2-(4-(3-(tert-butoxy)-2-(4-(tert-butyl)benzamido)-3-oxopropyl)phenyl)pyrimidine-5-carboxylic acidAusbeute 88 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 311Citric AcidLösungsmittelHCID 6228DimethylformamideLösungsmittel2×

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

Prepared using General Procedure 10. Into an oven-dried vial containing lithium formate (58 mg (1.1 mmol) in DMF (5 mL) were added DIEA (400 μL, 2.2 mmol) and acetic anhydride (210 μL, 2.2 mmol). After stirring for 1 h, the reaction mixture was degassed by N2 bubbling. A second, degassed solution containing (S)-tert-butyl 3-(4-(5-bromopyrimidin-2-yl)phenyl)-2-(4-(tert-butyl)benzamido)propanoate, INT-14 (200 mg, 0.4 mmol) and PdCl2(dppf) (27 mg, 0.04 mmol) in DMF (5 mL) was added via cannula. The resulting mixture was heated for 1 h at 120° C. in a microwave reactor. The reaction mixture was diluted with 10% citric acid and extracted with EA. The organic extract was dried (Na2SO4), concentrated, and purified by chromatography (EA/hexane) to provide 166 mg (88%) of (S)-2-(4-(3-(tert-butoxy)-2-(4-(tert-butyl)benzamido)-3-oxopropyl)phenyl)pyrimidine-5-carboxylic acid as a brown solid. LCMS-ESI (m/z) calculated for C29H33BN3O5: 503.6. found 504.2 [M+H]+, tR=3.87 min (Method 1). 1H NMR (400 MHz, CDCl3) δ 9.24 (s, 2H), 8.42 (d, J=8.2 Hz, 2H), 7.75 (t, J=11.9 Hz, 2H), 7.45 (d, J=8.4 Hz, 2H), 7.34 (d, J=8.2 Hz, 2H), 6.91 (t, J=11.5 Hz, 1H), 5.12 (dd, J=12.9, 5.5 Hz, 1H), 3.32 (qd, J=13.8, 5.4 Hz, 2H), 1.50 (s, 9H), 1.29 (d, J=29.8 Hz, 9H).

Aufarbeitung

  1. customPrepared
  2. customthe reaction mixture was degassed by N2 bubbling
  3. customA second, degassed solution
  4. additionwas added via cannula
  5. extractionextracted with EA
  6. extractionThe organic extract
  7. dry with materialwas dried (Na2SO4)
  8. concentrationconcentrated
  9. custompurified by chromatography (EA/hexane)

Quellen und Nachweise

ORD-Eintrag
ord-1426e87d89404076a74763172502636f
Quelldatensatz
uspto-grants-2016_02
Patentnummer
US09260427B2

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