(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 1028058ノート

反応式

HRID 1028058 の反応式
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

参加物

5

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 178418807HCID 178418807、化合物触媒HCID 80711,2-Dimethoxyethane溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-a4f3716e033f438184adb3f944d89d93
出典データセット
uspto-grants-2014_05
特許番号
US08735424B2

反応ノート

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