Water → 2,6-Difluoro-3-[4'-(4-methoxy-phenyl)-[2,5']bithiazolyl-2'-ylmethoxy]-benzamide

HRID 538522ノート

反応式

HRID 538522 の反応式
Br[C:2]1[S:6][C:5]([CH2:7][O:8][C:9]2[C:10]([F:19])=[C:11]([C:15]([F:18])=[CH:16][CH:17]=2)[C:12]([NH2:14])=[O:13])=[N:4][C:3]=1[C:20]1[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=1.C([Sn](CCCC)(CCCC)[C:33]1[S:34][CH:35]=[CH:36][N:37]=1)CCC.O>CN(C=O)C.[Pd].C1(P(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[F:19][C:10]1[C:9]([O:8][CH2:7][C:5]2[S:6][C:2]([C:33]3[S:34][CH:35]=[CH:36][N:37]=3)=[C:3]([C:20]3[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=3)[N:4]=2)=[CH:17][CH:16]=[C:15]([F:18])[C:11]=1[C:12]([NH2:14])=[O:13]

参加物

6

反応物 3

HCID 962WaterHCID 27632592-(Tributylstannyl)-1,3-thiazoleHCID 594026583-[5-Bromo-4-(4-methoxy-phenyl)-thiazol-2-ylmethoxy]-2,6-difluoro-benzamide

生成物 1

HCID 594027082,6-Difluoro-3-[4'-(4-methoxy-phenyl)-[2,5']bithiazolyl-2'-ylmethoxy]-benzamide収率 3.3%

試薬・触媒・溶媒 2

HCID 57646695Palladium;tetraphenyl-lambda5-phosphane触媒HCID 6228Dimethylformamide溶媒

反応条件

温度
120 °C

実験手順

To a solution of 3-[5-bromo-4-(4-methoxy-phenyl)-thiazol-2-ylmethoxy]-2,6-difluoro-benzamide (0.1 g, 0.2 mmol) in 5 ml of anhydrous DMF was added 2-tributylstannyl thiazole (0.071 g, 0.2 mmol) and degassed the reaction mixture for the 10 minutes. Then added tetraphenylphosphine palladium (0) (0.026 g, 0.2 mmol). The reaction mixture was heated at 120° C. for 12 h under the nitrogen atmosphere. Then reaction mixture was cooled to rt. 100 ml of water was added into it and extracted the compound with ethyl acetate, The combined organic layers were dried over anhydrous Na2SO4, and evaporated to dryness under reduced pressure. The compound was purified by column chromatography on silica (230-400μ) using ethyl acetate (40:60) as the eluent to provide the title compound as yellow solid (0.003 g, 3%). 1H NMR (DMSO-d6, 400 MHz): δ 3.82 (s, 3H), 5.57 (s, 2H), 7.06 (d, 1H, J=8.4 Hz (o-coupling), 7.13 (dt, 1H), 7.39-7.47 (m, 1H), 7.51 (d, 2H, J=8.4 Hz (o-coupling), 7.52-7.58 (m, 1H), 7.59-7.86 (m, 2H), 7.68 (d, 1H, J=3.2 Hz), 7.84 (d, 1H, J=3.2 Hz), 7.89 (broad s, 1H), 8.18 (broad s, 1H), 9.12 (s, 1H); MS ES+ (460.01), HPLC (method 5) Rt=15.64 min.

後処理

  1. customdegassed the reaction mixture for the 10 minutes
  2. customThen reaction mixture
  3. temperaturewas cooled to rt
  4. extractionextracted the compound with ethyl acetate
  5. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  6. customevaporated to dryness under reduced pressure
  7. customThe compound was purified by column chromatography on silica (230-400μ)

出典と根拠

ORDレコード
ord-d8500181b10a49ee98fefc16bf8d5736
出典データセット
uspto-grants-2014_10
特許番号
US08865736B2

反応ノート

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