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Water → 4-(5-Cyano-7-isopropyl-1,3-benzoxazol-2-yl)-N-({(3S)-1-[5-(2-isopropoxy-5-methylphenyl)pyridin-2-yl]pyrrolidin-3-yl}methyl)benzamide

HRID 2066836
ノート
印刷プレビュー

反応式

HRID 2066836 の反応式
C(=O)([O-])[O-].[Na+].[Na+].[CH:7]([O:10][C:11]1[CH:16]=[CH:15][C:14]([CH3:17])=[CH:13][C:12]=1B(O)O)([CH3:9])[CH3:8].Br[C:22]1[CH:23]=[CH:24][C:25]([N:28]2[CH2:32][CH2:31][C@@H:30]([CH2:33][NH:34][C:35](=[O:56])[C:36]3[CH:41]=[CH:40][C:39]([C:42]4[O:43][C:44]5[C:50]([CH:51]([CH3:53])[CH3:52])=[CH:49][C:48]([C:54]#[N:55])=[CH:47][C:45]=5[N:46]=4)=[CH:38][CH:37]=3)[CH2:29]2)=[N:26][CH:27]=1.O>C1(C)C=CC=CC=1.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.C(O)C>[C:54]([C:48]1[CH:49]=[C:50]([CH:51]([CH3:53])[CH3:52])[C:44]2[O:43][C:42]([C:39]3[CH:40]=[CH:41][C:36]([C:35]([NH:34][CH2:33][C@@H:30]4[CH2:31][CH2:32][N:28]([C:25]5[CH:24]=[CH:23][C:22]([C:12]6[CH:13]=[C:14]([CH3:17])[CH:15]=[CH:16][C:11]=6[O:10][CH:7]([CH3:9])[CH3:8])=[CH:27][N:26]=5)[CH2:29]4)=[O:56])=[CH:37][CH:38]=3)=[N:46][C:45]=2[CH:47]=1)#[N:55]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

8

反応物 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 35474222-Isopropoxy-5-methylphenylboronic acidHCID 25152256N-{[(3S)-1-(5-Bromopyridin-2-yl)pyrrolidin-3-yl]methyl}-4-(5-cyano-7-isopropyl-1,3-benzoxazol-2-yl)benzamide

生成物 1

HCID 251524514-(5-Cyano-7-isopropyl-1,3-benzoxazol-2-yl)-N-({(3S)-1-[5-(2-isopropoxy-5-methylphenyl)pyridin-2-yl]pyrrolidin-3-yl}methyl)benzamide
収率 75.6%

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒HCID 702Ethanol溶媒HCID 1140Toluene溶媒

反応条件

温度
150 °C

実験手順

Sodium carbonate (100 μl, 2M aqueous), (2-isopropoxy-5-methylphenyl)boronic acid (39 mg), and N-{[(3R)-1-(5-bromopyridin-2-yl)pyrrolidin-3-yl]methyl}-4-(5-cyano-7-isopropyl-1,3-benzoxazol-2-yl)benzamide (EXAMPLE 85, 27 mg) were dissolved in toluene (2.1 ml), water (0.6 ml) and ethanol (0.3 ml). To this solution was added tetrakis(triphenylphosphine)palladium(0) (9 mg). The mixture was heated to 150° C. for 25 min via microwave, and then cooled and concentrated. The residue was dissolved in dichloromethane, and purified via flash chromatography on a Biotage Horizon, 40 M column, eluting with 1 column volume of 100% hexanes, followed by a gradient of 0 to 100% ethyl acetate in hexanes over 10 column volumes, followed by 4 column volumes of 100% ethyl acetate to provide the title compound (23 mg, 74%). Mass spectrum (ESI) 614.6 (M+2). 1H NMR (500 MHz, CDCl3): δ 8.37 (d, J=2.3 Hz, 1H), 8.34 (d, J=8.2 Hz, 2H), 7.95 (d, J=8.2 Hz, 2H), 7.94 (s, 1H), 7.72 (dd, J=8.6 Hz, 2.3 Hz, 1H), 7.52 (s, 1H), 7.09 (s, 1H), 7.04 (dd, J=8.4 Hz, 2.1 Hz, 1H), 6.87 (d, J=8.2 Hz, 1H), 6.43 (d, J=8.7 Hz, 2H), 4.40 (sept, J=6.1 Hz, 1H), 3.79 (m, 2H), 3.73 (m, 1H), 3.51 (m, 3H), 3.41 (m, 1H), 2.76 (sept, J=6.9 Hz, 1H), 2.32 (s, 3H), 2.27 (m, 1H), 1.91, (m, 1H), 1.46 (d, J=6.8 Hz, 6H), 1.24 (d, J=5.9 Hz, 6H).

後処理

  1. temperaturecooled
  2. concentrationconcentrated
  3. dissolutionThe residue was dissolved in dichloromethane
  4. custompurified via flash chromatography on a Biotage Horizon, 40 M column
  5. washeluting with 1 column volume of 100% hexanes

出典と根拠

ORDレコード
ord-036c6c49845f4b048c9265ae2ea0f430
出典データセット
uspto-grants-2012_10
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08293721B2

反応ノート

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このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート