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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
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HRID 2066836 반응식
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]
참가 물질반응 조건실험 절차후처리출처 및 근거반응 노트

참가 물질

8

반응물 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

생성물 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
수율 75.6%

시약·촉매·용매 3

HCID 178418397HCID 178418397, 화합물촉매HCID 702Ethanol용매HCID 1140Toluene용매

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온도
150 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-036c6c49845f4b048c9265ae2ea0f430
출처 데이터셋
uspto-grants-2012_10
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08293721B2

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