(S)-tert-butyl 1-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinolin-4-yl)piperidin-3-ylcarbamate → (S)-1-(6-(6-(thiazol-2-yl)pyridin-2-yl)quinolin-4-yl)piperidin-3-amine

HRID 1028058Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1028058
CC1(C)C(C)(C)OB([C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][CH:18]=2)[N:15]=[CH:14][CH:13]=[C:12]3[N:19]2[CH2:24][CH2:23][CH2:22][C@H:21]([NH:25]C(=O)OC(C)(C)C)[CH2:20]2)O1.FC(F)(F)S(O[C:40]1[CH:45]=[CH:44][CH:43]=[C:42]([C:46]2[S:47][CH:48]=[CH:49][N:50]=2)[N:41]=1)(=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(Cl)Cl.COCCOC>[S:47]1[CH:48]=[CH:49][N:50]=[C:46]1[C:42]1[N:41]=[C:40]([C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][CH:18]=2)[N:15]=[CH:14][CH:13]=[C:12]3[N:19]2[CH2:24][CH2:23][CH2:22][C@H:21]([NH2:25])[CH2:20]2)[CH:45]=[CH:44][CH:43]=1

Komponenten

5

Edukt 2

HCID 67316377(S)-tert-butyl 1-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinolin-4-yl)piperidin-3-ylcarbamateHCID 866564566-(Thiazol-2-yl)pyridin-2-yl trifluoromethanesulfonate

Produkt 1

HCID 58387574(S)-1-(6-(6-(thiazol-2-yl)pyridin-2-yl)quinolin-4-yl)piperidin-3-amineAusbeute 40 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418807HCID 178418807, VerbindungKatalysatorHCID 80711,2-DimethoxyethaneLösungsmittel

Versuchsvorschrift

A solution of (S)-tert-butyl 1-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinolin-4-yl)piperidin-3-ylcarbamate (1.0 equiv.), 6-(thiazol-2-yl)pyridin-2-yl trifluoromethanesulfonate (1.5 equiv.) and Pd(dppf)Cl2—CH2Cl2 (0.15 equiv.) in 3:1 DME/2M Na2CO3 was heated in a microwave at 100° C. for 20 minutes. Upon cooling, the solution was partitioned between EtOAc and Na2CO3(sat.) washed further with NaCl(sat.), dried over MgSO4, concentrated and purified by RP HPLC. Upon lyophilization, the Boc group was deprotected by treatment with 25% TFA/CH2Cl2, concentrated, purified by RP-HPLC and lyophilized to yield (S)-1-(6-(6-(thiazol-2-yl)pyridin-2-yl)quinolin-4-yl)piperidin-3-amine (40%). LC/MS=388.1 (M+H), LC=2.02 min.

Aufarbeitung

  1. temperatureUpon cooling
  2. customthe solution was partitioned between EtOAc and Na2CO3(sat.)
  3. washwashed further with NaCl(sat.)
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. custompurified by RP HPLC
  7. concentrationconcentrated
  8. custompurified by RP-HPLC

Quellen und Nachweise

ORD-Eintrag
ord-a4f3716e033f438184adb3f944d89d93
Quelldatensatz
uspto-grants-2014_05
Patentnummer
US08735424B2

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