(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 1028058Notes

Reaction equation

HRID 1028058 reaction equation
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

Participants

5

Reactant 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

Product 1

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

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-a4f3716e033f438184adb3f944d89d93
Source dataset
uspto-grants-2014_05
Patent number
US08735424B2

Reaction notes

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