Phenylacetic Acid → N-Cyclopropyl-2-phenyl-N-[4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-thiazol-2-yl]-acetamide

HRID 2108733

反応式

HRID 2108733 の反応式
[CH:1]1([NH:4][C:5]2[S:6][CH:7]=[C:8]([C:10]3[C:18]4[C:13](=[N:14][CH:15]=[CH:16][CH:17]=4)[NH:12][CH:11]=3)[N:9]=2)[CH2:3][CH2:2]1.[C:19]1([CH2:25][C:26](O)=[O:27])[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C(N(CC)CC)C>CN(C=O)C.C1COCC1>[CH:1]1([N:4]([C:5]2[S:6][CH:7]=[C:8]([C:10]3[C:18]4[C:13](=[N:14][CH:15]=[CH:16][CH:17]=4)[NH:12][CH:11]=3)[N:9]=2)[C:26](=[O:27])[CH2:25][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH2:3][CH2:2]1

参加物

5

反応物 3

HCID 999Phenylacetic AcidHCID 8471TriethylamineHCID 11615827cyclopropyl-[4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-thiazol-2-yl]-amine

生成物 1

HCID 11552526N-Cyclopropyl-2-phenyl-N-[4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-thiazol-2-yl]-acetamide収率 12.3%

試薬・触媒・溶媒 1

HCID 21974620tetrahydrofuran N,N-dimethylformamide溶媒

反応条件

温度
180 °C

実験手順

Cyclopropyl-[4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-thiazol-2-yl]-amine (50 mg, 0.39 mmol), phenylacetic acid (63 mg, 0.47 mmol) and N-(1-methanesulfonyl)benzotriazole (93 mg, 0.47 mmol) were placed in a microwave reaction vessel (Personal Chemistry, Uppsala, Sweden). 5% DMF-THF (4 mL) was added followed by triethylamine (0.163 mL, 1.17 mmol) and the mixture heated in the sealed tube at 180° C. for 15 minutes. Upon cooling to room temperature the reaction was concentrated and then purified by prepartative TLC (thin layer chromatography) and eluted with ethylacetate and hexane (3:1). Extraction of the silica gel with 5% MeOH-EtOAc was carried out to give product (15 mg, 10%). Alternatively, Cyclopropyl-[4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-thiazol-2-yl]-amine (50 mg, 0.39 mmol), phenylacetic acid (63 mg, 0.47 mmol) and fluoro-N,N′,N′,N′-tetramethylformamidiniun hexafluorophosphate (148 mg, 0.59 mmol) were placed in a microwave reaction vessel (Personal Chemistry, Uppsala, Sweden). 5% DMF-THF (4 mL) was added followed by triethylamine (0.163 mL, 1.17 mmol) and the mixture heated in the sealed tube at 180° C. for 15 minutes. Upon cooling to room temperature the reaction was concentrated and then purified by prepartative TLC (thin layer chromatography) and eluted with ethylacetate and hexane (3:1). Extraction of the silica gel with 5% MeOH-EtOAc was carried out to give product (18 mg, 12%). The material was isolated as an HCl salt. LC/MS MH+ =375.2, LC/MS RT: 3.39 min. 1H NMR (500 MHz, DMSO-d6, ppm) 11.92 (s,1H), 8.63 (d,1H, J=7.88 Hz), 8.29 (dd,1H, J=4.71, 1.49 Hz), 8.96 (d,J=2.58,1H), 7.44 (s,1H), 7.36-7.19 (m,6H), 4.27 (s,2H), 3.29 (t, 1H,J=3.78), 1.33 (m,2H), 1.06 (m,2H).

後処理

  1. temperatureUpon cooling to room temperature the reaction
  2. concentrationwas concentrated
  3. custompurified by prepartative TLC (thin layer chromatography)
  4. washeluted with ethylacetate and hexane (3:1)
  5. extractionExtraction of the silica gel with 5% MeOH-EtOAc

出典と根拠

ORDレコード
ord-088d2c1d607b45a1a3788d038c2d3110
出典データセット
uspto-grants-2009_04
特許番号
US07514448B2

関連ノート

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