Sodium Bicarbonate → {4-[2-(4-methoxyphenyl)-pyrimidin-4-yl]-phenyl}-carbamic acid (2S,3R,4R,5S,6S)-3,4,5-trimethoxy-6-methyl-tetrahydropyran-2-yl ester

HRID 1925439Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1925439
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:14]=[C:13]([C:15]3[CH:20]=[CH:19][C:18]([NH2:21])=[CH:17][CH:16]=3)[CH:12]=[CH:11][N:10]=2)=[CH:5][CH:4]=1.C[Si](C)(C)[N-][Si](C)(C)C.[K+].[CH3:32][O:33][CH:34]1[CH:39]([O:40][CH3:41])[CH:38]([O:42][CH3:43])[CH:37]([CH3:44])[O:36][CH:35]1[O:45][C:46](=O)[O:47]C1C=CC([N+]([O-])=O)=CC=1.C(=O)(O)[O-].[Na+]>C1COCC1.C1(C)C=CC=CC=1>[CH3:32][O:33][C@@H:34]1[C@H:39]([O:40][CH3:41])[C@@H:38]([O:42][CH3:43])[C@H:37]([CH3:44])[O:36][C@H:35]1[O:45][C:46](=[O:47])[NH:21][C:18]1[CH:19]=[CH:20][C:15]([C:13]2[CH:12]=[CH:11][N:10]=[C:9]([C:6]3[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=3)[N:14]=2)=[CH:16][CH:17]=1

Komponenten

7

Edukt 4

HCID 516892Sodium BicarbonateHCID 3251421Potassium bis(trimethylsilyl)amideHCID 67519234Carbonic acid 4-nitrophenyl ester 3,4,5-trimethoxy-6-methyl-tetrahydropyran-2-yl esterHCID 675194204-[2-(4-Methoxyphenyl)-pyrimidin-4-yl]-phenylamine

Produkt 1

HCID 44230218{4-[2-(4-methoxyphenyl)-pyrimidin-4-yl]-phenyl}-carbamic acid (2S,3R,4R,5S,6S)-3,4,5-trimethoxy-6-methyl-tetrahydropyran-2-yl esterAusbeute 8,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 1140TolueneLösungsmittelHCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

To a mixture cooled in an ice bath of 112 mg (0.404 mmol) of 4-[2-(4-methoxyphenyl)-pyrimidin-4-yl]-phenylamine in 1.5 mL of dry THF was added dropwise via syringe 0.81 mL (0.40 mmol) of a 0.5 M solution of potassium hexamethyldisilazide in toluene over a 10-15 minute period. This solution was then added dropwise via syringe to a solution cooled in an ice bath of 126 mg (0.386 mmol) of carbonic acid 4-nitrophenyl ester 3,4,5-trimethoxy-6-methyl-tetrahydropyran-2-yl ester in 2 mL of THF. The contents were allowed to gradually warm to room temperature and stir overnight and were added to cold saturated sodium bicarbonate. The mixture was extracted two times with ethyl ether and the combined extracts were dried (MgSO4). Concentration gave a red oil which was purified by chromatography on silica gel using 1:1 hexanes/EtOAc to afford 16 mg (8%) of Compound 234. 1H NMR (300 MHz, CDCl3) δ 8.79 (d, J=5.2 Hz, 1H), 8.55 (d, J=8.8 Hz, 2H), 8.25 (d, J=8.8 Hz, 2H), 7.62 (d, J=8.5 Hz, 2H), 7.53 (d, J=5.5 Hz, 1H), 7.05 (d, J=9.0 Hz, 2H), 6.84 (br s, 1H), 6.26 (d, J=1.7 Hz, 1H), 3.92 (s, 3H), 3.71-3.69 (m, 2H), 3.61 (s, 3H), 3.60 (s, 3H), 3.57 (s, 3H), 3.55-3.47 (m, 1H), 3.24 (t, J=9.4 Hz, 1H), 1.36 (d, J=6.1 Hz, 3H); MS (API-ES+) 510 ([M+H]+, 100).

Aufarbeitung

  1. additionThis solution was then added dropwise via syringe to a solution
  2. extractionThe mixture was extracted two times with ethyl ether
  3. dry with materialthe combined extracts were dried (MgSO4)
  4. concentrationConcentration
  5. customgave a red oil which
  6. customwas purified by chromatography on silica gel using 1:1 hexanes/EtOAc

Quellen und Nachweise

ORD-Eintrag
ord-575d0afc72264a57a5c859c016274d9a
Quelldatensatz
uspto-grants-2012_05
Patentnummer
US08178658B2

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