1,2-Dimethoxyethane → (4-(7-(4-Amino-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)phenyl)(morpholino)methanone

HRID 1676324

反応式

HRID 1676324 の反応式
[F:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1[O:9][C:10]1[CH:15]=[CH:14][N:13]=[C:12]2[CH:16]=[C:17](I)[S:18][C:11]=12)[NH2:5].C(=O)([O-])[O-].[Cs+].[Cs+].[N:26]1([C:32]([C:34]2[CH:39]=[CH:38][C:37](B(O)O)=[CH:36][CH:35]=2)=[O:33])[CH2:31][CH2:30][O:29][CH2:28][CH2:27]1.COCCOC>O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:5][C:4]1[CH:6]=[CH:7][C:8]([O:9][C:10]2[CH:15]=[CH:14][N:13]=[C:12]3[CH:16]=[C:17]([C:37]4[CH:36]=[CH:35][C:34]([C:32]([N:26]5[CH2:31][CH2:30][O:29][CH2:28][CH2:27]5)=[O:33])=[CH:39][CH:38]=4)[S:18][C:11]=23)=[C:2]([F:1])[CH:3]=1

参加物

7

反応物 4

HCID 80711,2-DimethoxyethaneHCID 10796Cesium carbonateHCID 2773546[4-(Morpholine-4-carbonyl)phenyl]boronic acidHCID 584749503-Fluoro-4-((2-iodothieno[3,2-b]pyridin-7-yl)oxy)aniline

生成物 1

HCID 67347265(4-(7-(4-Amino-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)phenyl)(morpholino)methanone収率 13.3%

試薬・触媒・溶媒 2

HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒

反応条件

温度
85 °C

実験手順

A sealable tube was charged with 3-fluoro-4-(2-iodothieno[3,2-b]pyridin-7-yloxy)aniline (Example 6, Step A, 0.200 g, 0.518 mmol), cesium carbonate (0.253 g, 0.777 mmol), 4-(morpholine-4-carbonyl)phenylboronic acid (0.183 g, 0.777 mmol) and DME (2 mL). The mixture was degassed under nitrogen for 10 minutes and Pd(PPh3)4 (0.0299 g, 0.0259 mmol) was added as a solid. The mixture was heated to 85° C. for 18 hours. The crude was diluted with water (300 mL), extracted with EtOAc/MeOH (4:1, 2×300 mL), dried organic over sodium sulfate, filtered and concentrated. The crude product was purified by preparative TLC (2.0 mm thickness) eluting with EtOAc/MeOH (9:1) to give product (31 mg, 12%) as a white solid. LRMS (APCI+) 450 m/z (M+1) detected.

後処理

  1. customThe mixture was degassed under nitrogen for 10 minutes
  2. extractionextracted with EtOAc/MeOH (4:1, 2×300 mL), dried organic over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude product was purified by preparative TLC (2.0 mm thickness)
  6. washeluting with EtOAc/MeOH (9:1)

出典と根拠

ORDレコード
ord-a7094c19d4d347a49b907ffef16ad68e
出典データセット
uspto-grants-2011_08
特許番号
US08003662B2

関連ノート

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