Reaktion #966586

Reaktionsgleichung

(S)-ethyl 2-(2-bromo-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-tert-butoxyacetate

5,6,7,8-tetrahydro-1,6-naphthyridine, dihydrochloride

NaOH

KOH

→

desired product

(S)-2-tert-butoxy-2-(7-(4-chlorophenyl)-2-(7,8-dihydro-1,6-naphthyridin-6(5H)-yl)-5-methylbenzo[d]thiazol-6-yl)acetic acid

Lösungsmittel

N,N-dimethylacetamide

DCM

H2O

EtOH

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe organic phase was collected
2. 2
   Trocknendried with a small amount of Na2SO4
3. 3
   Sonstigedecanted
4. 4
   Einengenconcentrated
5. 5
   Sonstigeto give the free base
6. 6
   SonstigeThe vessel was sealed
7. 7
   TemperaturThe reaction was heated to 100° C. for 30 min
8. 8
   TemperaturThe reaction was cooled to 23° C.
9. 9
   Filtrationfiltered
10. 10
    Filtration(0.45 micron teflon syringe filter)
11. 11
    SonstigeThe filtrate was purified by reverse phase HPLC
12. 12
    Wascheneluting by 5-100% acetonitrile in H2O with 0.1% TFA

Vorschrift

A vial was charged with 5,6,7,8-tetrahydro-1,6-naphthyridine, dihydrochloride, hydrate (125 mg), DCM (1.5 mL), and 50% w/v aq KOH (200 μL). The vial was shaken. Then H2O (1.3 mL) was added. The organic phase was collected, dried with a small amount of Na2SO4, decanted, and concentrated to give the free base. N,N-dimethylacetamide (500 μL), and (S)-ethyl 2-(2-bromo-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-tert-butoxyacetate (25 mg, 50 μmol) were added. The vessel was sealed and heated to 100° C. for 30 min. Then THF (1 mL), EtOH (absolute, 500 μL), and 5 M aq NaOH (500 μL) were added. The reaction was heated to 100° C. for 30 min. The reaction was cooled to 23° C., and filtered (0.45 micron teflon syringe filter). The filtrate was purified by reverse phase HPLC, eluting by 5-100% acetonitrile in H2O with 0.1% TFA to give the desired product. LCMS-ESI+: calc'd for C28H28ClN3O3S: 522.2, 524.2 (M+H+); Found: 522.3, 524.2 (M+H+). NMR (400 MHz, CD3OD): δ 8.62 (d, J=5.6 Hz, 1H), 8.29 (d, J=8.1 Hz, 1H), 7.78 (dd, J=7.9, 5.6 Hz, 1H), 7.63 (dd, J=8.5, 1.9 Hz, 1H), 7.58-7.52 (m, 2H), 7.52-7.44 (m, 1H), 7.38 (app. s, 1H), 5.15 (s, 1H), 4.96 (s, broad, 2H), 4.03 (t, J=5.9 Hz, 2H), 3.31-3.23 (m, 2H), 2.51 (s, 3H), 0.95 (s, 9H).

Quelle