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Water → Ethyl 2-(2-(3-aminophenyl)-5-(1-(4-(1,3-dioxoisoindolin-2-yl)butyl)-3-fluoro-2-phenyl-1H-indole-6-carbonyl)thiophen-3-yl)acetate

HRID 1952511
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HRID 1952511 반응식
Br[C:2]1[S:3][C:4]([C:13]([C:15]2[CH:23]=[C:22]3[C:18]([C:19]([F:45])=[C:20]([C:39]4[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=4)[N:21]3[CH2:24][CH2:25][CH2:26][CH2:27][N:28]3[C:36](=[O:37])[C:35]4[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=4)[C:29]3=[O:38])=[CH:17][CH:16]=2)=[O:14])=[CH:5][C:6]=1[CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9].[F-].[Cs+].[NH2:48][C:49]1[CH:50]=[C:51](B(O)O)[CH:52]=[CH:53][CH:54]=1.O>COCCOC.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>[NH2:48][C:49]1[CH:54]=[C:53]([C:2]2[S:3][C:4]([C:13]([C:15]3[CH:23]=[C:22]4[C:18]([C:19]([F:45])=[C:20]([C:39]5[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=5)[N:21]4[CH2:24][CH2:25][CH2:26][CH2:27][N:28]4[C:36](=[O:37])[C:35]5[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=5)[C:29]4=[O:38])=[CH:17][CH:16]=3)=[O:14])=[CH:5][C:6]=2[CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH:52]=[CH:51][CH:50]=1
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

7

반응물 4

HCID 962WaterHCID 25953Cesium fluorideHCID 922693-Aminophenylboronic acidHCID 67496700Ethyl 2-(2-bromo-5-(1-(4-(1,3-dioxoisoindolin-2-yl)butyl)-3-fluoro-2-phenyl-1H-indole-6-carbonyl)thiophen-3-yl)acetate

생성물 1

HCID 67496828Ethyl 2-(2-(3-aminophenyl)-5-(1-(4-(1,3-dioxoisoindolin-2-yl)butyl)-3-fluoro-2-phenyl-1H-indole-6-carbonyl)thiophen-3-yl)acetate
수율 76.4%

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 80711,2-Dimethoxyethane용매

실험 절차

A mixture of 6 (40 mg, 0.058 mmol), Pd(PPh3)4 (13 mg, 0.011 mmol), CsF (27 mg, 0.18 mmol), 3-aminophenylboronic acid (12 mg, 0.088 mmol), and H2O (80 μL) in DME (8 mL) was degassed with N2 for 10 minutes and then refluxed. When the reaction was over by TLC monitoring, the mixture was poured into H2O (10 mL) and then extracted with 70 mL Et2O. The organic layer was washed with brine (2×10 mL), dried over MgSO4, and then concentrated in vacuo. MPLC purification (Hex:EtOAc/5:1) of the residue gave 7 as a yellow amorphous solid (31 mg, 76%). 1H NMR (400 MHz, CDCl3) δ 8.00 (s, 1H), 7.78-7.67 (m, 7H), 7.51-7.41 (m, 5H), 7.23 (t, J=8.0 Hz, 1H), 6.90 (d, J=7.6 Hz, 1H), 6.85 (s, 1H), 6.73 (d, J=8.0 Hz, 1H), 4.26 (t, J=7.0 Hz, 2H), 4.15 (q, J=7.2 Hz, 2H), 3.82 (brs, 2H), 3.70 (s, 2H), 3.48 (t, J=6.8 Hz, 2H), 1.66-1.60 (m, 2H), 1.48-1.45 (m, 2H), and 1.25 (t, J=7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 188.13, 171.26, 168.49, 149.66, 147.09, 143.16, 141.68, 140.71, 137.58, 134.19, 132.51, 132.44, 132.38, 132.14, 130.54, 130.05, 129.97, 129.54, 129.15, 129.06, 128.94, 128.58, 127.31, 127.10, 123.47, 121.43, 120.02, 119.86, 119.71, 116.81, 115.88, 115.69, 112.56, 61.31, 43.61, 37.25, 34.77, 27.36, 25.77, and 14.45; 19F NMR (376 MHZ, CDCl3) δ −174.49.

후처리

  1. customwas degassed with N2 for 10 minutes
  2. temperaturerefluxed
  3. additionthe mixture was poured into H2O (10 mL)
  4. extractionextracted with 70 mL Et2O
  5. washThe organic layer was washed with brine (2×10 mL)
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated in vacuo
  8. customMPLC purification (Hex:EtOAc/5:1) of the residue

출처 및 근거

ORD 기록
ord-b00440db0abe4f51b41b0b1930a692dd
출처 데이터셋
uspto-grants-2013_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08404728B2

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