(6-Methoxypyridin-3-yl)(thiazol-5-yl)methanone → (3-(4-(1H-Pyrazol-1-yl)benzyl)-4-chloro-2-methoxyquinolin-6-yl)(6-methoxypyridin-3-yl)(thiazol-5-yl)methanol

HRID 928831

反応式

HRID 928831 の反応式
C([Li])CCC.[N:6]1([C:11]2[CH:31]=[CH:30][C:14]([CH2:15][C:16]3[C:17]([O:28][CH3:29])=[N:18][C:19]4[C:24]([C:25]=3[Cl:26])=[CH:23][C:22](Br)=[CH:21][CH:20]=4)=[CH:13][CH:12]=2)[CH:10]=[CH:9][CH:8]=[N:7]1.[CH3:32][O:33][C:34]1[N:39]=[CH:38][C:37]([C:40]([C:42]2[S:46][CH:45]=[N:44][CH:43]=2)=[O:41])=[CH:36][CH:35]=1>C1COCC1>[N:6]1([C:11]2[CH:31]=[CH:30][C:14]([CH2:15][C:16]3[C:17]([O:28][CH3:29])=[N:18][C:19]4[C:24]([C:25]=3[Cl:26])=[CH:23][C:22]([C:40]([C:37]3[CH:38]=[N:39][C:34]([O:33][CH3:32])=[CH:35][CH:36]=3)([C:42]3[S:46][CH:45]=[N:44][CH:43]=3)[OH:41])=[CH:21][CH:20]=4)=[CH:13][CH:12]=2)[CH:10]=[CH:9][CH:8]=[N:7]1

参加物

5

反応物 3

HCID 86715595(6-Methoxypyridin-3-yl)(thiazol-5-yl)methanone2 回HCID 867155963-(4-(1H-Pyrazol-1-yl)benzyl)-6-bromo-4-chloro-2-methoxyquinoline2 回HCID 178418339Butyllithium

生成物 1

HCID 86715663(3-(4-(1H-Pyrazol-1-yl)benzyl)-4-chloro-2-methoxyquinolin-6-yl)(6-methoxypyridin-3-yl)(thiazol-5-yl)methanol

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
0 °C

実験手順

n-Butyllithium (0.154 mL, 0.246 mmol; 1.6 M in hexane) was added dropwise to a solution of 3-(4-(1H-pyrazol-1-yl)benzyl)-6-bromo-4-chloro-2-methoxyquinoline (0.081 g, 0.189 mmol, Intermediate 16) in dry THF (4 mL) at −78° C. over a 5 minute period. After complete addition stirring was continued at −78° C. for 30 minutes then (6-methoxypyridin-3-yl)(thiazol-5-yl)methanone (0.046 g, 0.189 mmol, Intermediate 15) dissolved in THF (1.9 mL) was slowly added and the reaction warmed in an ice bath to 0° C. The mixture was stirred for 30 minutes, quenched with saturated aqueous NH4Cl then warmed to room temperature. After stirring for 10 minutes layers were separated and the aqueous layer extracted with EtOAc. The combined organic extracts were dried over Na2SO4, filtered, evaporated in vacuo and chromatographed (0-100% EtOAc in DCM) to provide the title compound. 1H NMR (400 MHz, MeOH-d4) δ ppm 3.94 (s, 3H) 4.08 (s, 3H) 4.35 (s, 2H) 6.43-6.52 (m, 1H) 6.88 (d, J=9.09 Hz, 1H) 7.37 (d, J=8.08 Hz, 2H) 7.54-7.63 (m, 3H) 7.66-7.72 (m, 2H) 7.77 (dd, J=8.59, 2.53 Hz, 1H) 7.85 (d, J=8.59 Hz, 1H) 8.12 (dd, J=13.14, 2.53 Hz, 2H) 8.20 (s, 1H) 9.08 (s, 1H); MS (ESI) 570.

後処理

  1. additionAfter complete addition
  2. additionwas slowly added
  3. stirringThe mixture was stirred for 30 minutes
  4. customquenched with saturated aqueous NH4Cl
  5. temperaturethen warmed to room temperature
  6. stirringAfter stirring for 10 minutes layers
  7. customwere separated
  8. extractionthe aqueous layer extracted with EtOAc
  9. dry with materialThe combined organic extracts were dried over Na2SO4
  10. filtrationfiltered
  11. customevaporated in vacuo
  12. customchromatographed (0-100% EtOAc in DCM)

出典と根拠

ORDレコード
ord-fb267525925642e2b5b74c9725a11b7a
出典データセット
uspto-grants-2016_03
特許番号
US09290476B2

関連ノート

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