Cesium carbonate → [4-Difluoromethoxy-2-ethyl-8-fluoro-3-(4-pyrimidin-2-yl-benzyl)quinolin-5-yloxy]acetic acid

HRID 1922089ノート

反応式

HRID 1922089 の反応式
C[O:2][C:3](=[O:39])[CH2:4][O:5][C:6]1[CH:15]=[CH:14][C:13]([F:16])=[C:12]2[C:7]=1[C:8]([O:35][CH:36]([F:38])[F:37])=[C:9]([CH2:19][C:20]1[CH:25]=[CH:24][C:23](B3OC(C)(C)C(C)(C)O3)=[CH:22][CH:21]=1)[C:10]([CH2:17][CH3:18])=[N:11]2.Br[C:41]1[N:46]=[CH:45][CH:44]=[CH:43][N:42]=1.O1CCOCC1.C(=O)([O-])[O-].[Cs+].[Cs+]>C(OCC)(=O)C.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]>[F:38][CH:36]([F:37])[O:35][C:8]1[C:7]2[C:12](=[C:13]([F:16])[CH:14]=[CH:15][C:6]=2[O:5][CH2:4][C:3]([OH:2])=[O:39])[N:11]=[C:10]([CH2:17][CH3:18])[C:9]=1[CH2:19][C:20]1[CH:21]=[CH:22][C:23]([C:41]2[N:46]=[CH:45][CH:44]=[CH:43][N:42]=2)=[CH:24][CH:25]=1

参加物

7

反応物 4

HCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 783452-BromopyrimidineHCID 67458783{4-Difluoromethoxy-2-ethyl-8-fluoro-3-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)benzyl]quinolin-5-yloxy}acetic acid methyl ester

生成物 1

HCID 25096075[4-Difluoromethoxy-2-ethyl-8-fluoro-3-(4-pyrimidin-2-yl-benzyl)quinolin-5-yloxy]acetic acid収率 23.7%

試薬・触媒・溶媒 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
110 °C

実験手順

A mixture of {4-difluoromethoxy-2-ethyl-8-fluoro-3-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)benzyl]quinolin-5-yloxy}acetic acid methyl ester (0.10 g), 2-bromopyrimidine (0.076 g), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium (0.016 g), 1,4-dioxane (2.0 mL) and 2.0 M aqueous cesium carbonate solution (0.38 mL) was heated by microwave irradiation at 90 to 130° C. for 1 hour. The mixture was cooled to room temperature, diluted with ethyl acetate and then filtered. The filtrate was concentrated under reduced pressure and the residue dissolved in tetrahydrofuran (5.0 mL) and 1.0 M aqueous lithium hydroxide solution (0.38 mL), and the resulting mixture was stirred at room temperature for 1 hour. The mixture was acidified by the addition of 0.1 M aqueous hydrochloric acid solution and then concentrated under reduced pressure. Purification of the residue by preparative reverse-phase HPLC gave title compound (0.021 g).

後処理

  1. temperatureThe mixture was cooled to room temperature
  2. filtrationfiltered
  3. concentrationThe filtrate was concentrated under reduced pressure
  4. dissolutionthe residue dissolved in tetrahydrofuran (5.0 mL)
  5. additionThe mixture was acidified by the addition of 0.1 M aqueous hydrochloric acid solution
  6. concentrationconcentrated under reduced pressure
  7. customPurification of the residue by preparative reverse-phase HPLC

出典と根拠

ORDレコード
ord-fee6ad59a9f9497db09df21599f9b02c
出典データセット
uspto-grants-2012_05
特許番号
US08173812B2

反応ノート

読み込み中…