Chloroform → 5-Amino-5-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]azepan-2-one

HRID 1040215Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1040215
CC(S([NH:7][C:8]1([C:18]2[S:19][C:20]([C:23]3[CH:28]=[C:27]([NH:29][C:30]4[N:35]=[C:34]([C:36]([F:39])([F:38])[F:37])[CH:33]=[CH:32][N:31]=4)[CH:26]=[C:25]([CH3:40])[CH:24]=3)=[CH:21][N:22]=2)[CH2:17][CH2:16][C:11]2(OCC[O:12]2)[CH2:10][CH2:9]1)=O)(C)C.C(Cl)(Cl)Cl.[N-:45]=[N+]=[N-].[Na+].CS(O)(=O)=O>O>[NH2:7][C:8]1([C:18]2[S:19][C:20]([C:23]3[CH:28]=[C:27]([NH:29][C:30]4[N:35]=[C:34]([C:36]([F:39])([F:38])[F:37])[CH:33]=[CH:32][N:31]=4)[CH:26]=[C:25]([CH3:40])[CH:24]=3)=[CH:21][N:22]=2)[CH2:17][CH2:16][NH:45][C:11](=[O:12])[CH2:10][CH2:9]1

Komponenten

6

Edukt 4

HCID 6212ChloroformHCID 6395Methanesulfonic AcidHCID 33557Sodium AzideHCID 672609322-methyl-N-{8-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]-1,4-dioxaspiro[4.5]dec-8-yl}propane-2-sulfinamide

Produkt 1

HCID 584562585-Amino-5-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]azepan-2-oneAusbeute 66 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
65 °C

Versuchsvorschrift

To the product of Step 2 (100 mg, 0.13 mmol) was added chloroform (630 pt), sodium azide (24.5 mg, 0.38 mmol), and methanesulfonic acid (98 μL, 1.51 mmol). The mixture was heated to 65° C. for 1.5 h., cooled to room temperature, diluted with water, and extracted with ethyl acetate (2×). The combined organic layers were dried over sodium sulfate, filtered, and concentrated. The residue was purified by reverse phase HPLC (35:65 to 70:30 acetonitrile:water with a 0.1% trifluoroacetic acid modifier). The fractions containing the desired product were diluted with ethyl acetate and free based with saturated aqueous sodium bicarbonate. The separated organic layer was dried over magnesium sulfate, filtered and concentrated to afford the title compound (38 mg, 0.083 mmol, 66% yield) as an orange oil. MS ESI: [M+H]+ m/z 463. 1H NMR (500 MHz, DMSO-d6) δ 10.26 (s, 1H), 8.83 (s, 1H), 8.75 (s, 1H), 8.02 (s, 1H), 7.93 (s, 1H), 7.49 (s, 1H), 7.28 (d, J=4.7, 1H), 7.16 (s, 1H), 2.39-2.08 (m, 9H), 1.30-0.99 (m, 4H). rhSYK activity=+++

Aufarbeitung

  1. temperaturecooled to room temperature
  2. extractionextracted with ethyl acetate (2×)
  3. dry with materialThe combined organic layers were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by reverse phase HPLC (35:65 to 70:30 acetonitrile
  7. additionThe fractions containing the desired product
  8. additionwere diluted with ethyl acetate
  9. dry with materialThe separated organic layer was dried over magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-9c87ba9fc97744a180976d4422f45b2e
Quelldatensatz
uspto-grants-2013_10
Patentnummer
US08551984B2

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