Diisopropylethylamine → N-(3-(6-(4-(1,4-Dimethyl-3-oxopiperazin-2-yl)phenylamino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methylphenyl)-7-oxo-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide

HRID 888435Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 888435
[NH2:1][C:2]1[C:3]([CH3:32])=[C:4]([C:8]2[N:9]=[C:10]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([CH:23]4[C:28](=[O:29])[N:27]([CH3:30])[CH2:26][CH2:25][N:24]4[CH3:31])=[CH:19][CH:18]=3)[C:11](=[O:15])[N:12]([CH3:14])[CH:13]=2)[CH:5]=[CH:6][CH:7]=1.[O:33]=[C:34]1[C:39]2[S:40][C:41]([C:43](O)=[O:44])=[CH:42][C:38]=2[CH2:37][CH2:36][CH2:35]1.C(N(CC)C(C)C)(C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>O.CN(C=O)C>[CH3:31][N:24]1[CH2:25][CH2:26][N:27]([CH3:30])[C:28](=[O:29])[CH:23]1[C:20]1[CH:19]=[CH:18][C:17]([NH:16][C:10]2[C:11](=[O:15])[N:12]([CH3:14])[CH:13]=[C:8]([C:4]3[C:3]([CH3:32])=[C:2]([NH:1][C:43]([C:41]4[S:40][C:39]5[C:34](=[O:33])[CH2:35][CH2:36][CH2:37][C:38]=5[CH:42]=4)=[O:44])[CH:7]=[CH:6][CH:5]=3)[N:9]=2)=[CH:22][CH:21]=1

Komponenten

7

Edukt 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 576251475-(3-Amino-2-methylphenyl)-3-(4-(1,4-dimethyl-3-oxopiperazin-2-yl)phenylamino)-1-methylpyrazin-2(1H)-oneHCID 576251597-Oxo-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxylic Acid

Produkt 1

HCID 25234214N-(3-(6-(4-(1,4-Dimethyl-3-oxopiperazin-2-yl)phenylamino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methylphenyl)-7-oxo-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamideAusbeute 52,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

A 50-mL single-neck round-bottomed flask equipped with a magnetic stirrer was purged with nitrogen and charged with 15 (249 mg, 1.27 mmol), 16 (500 mg, 1.16 mmol), N,N-diisopropylethylamine (600 mg, 4.64 mmol) and anhydrous DMF (5 mL). Benzotriazol-1-yl-oxy-tris(dimethylamino)phosphonium hexafluorophosphate (BOP, 616 mg, 1.39 mmol) was added, and the reaction was stirred for 4 h. After this time, the reaction was diluted with water (10 mL), and the resulting suspension was filtered. The filter cake was dissolved in methylene chloride (20 mL), and the solution was washed with 10% aqueous citric acid (10 mL), saturated aqueous sodium bicarbonate (10 mL), and water (10 mL), and dried over sodium sulfate. The drying agent was removed by filtration, and the solvent was evaporated under reduced pressure. The resulting residue was purified by flash chromatography to afford a 52% yield of 17 (370 mg) as a white solid: mp 154-155° C.; 1H NMR (500 MHz, CD2Cl2) δ 8.31 (s, 1H), 7.81 (dd, 1H, J=7.5, 1.5 Hz), 7.76-7.72 (m, 3H), 7.50 (s, 1H), 7.28-7.23 (m, 4H), 6.73 (s, 1H), 3.64 (td, 1H, J=11.5, 4.5 Hz), 3.57 (s, 1H), 3.55 (s, 3H), 3.14 (dt, 1H, J=11.5, 3.5 Hz), 2.93 (m, 1H), 2.88-2.86 (m, 5H), 2.62-2.57 (m, 3H), 2.36 (s, 3H), 2.17 (m, 2H), 2.09 (s, 3H); MS (ESI+) m/z 611.2 (M+H).

Aufarbeitung

  1. customA 50-mL single-neck round-bottomed flask equipped with a magnetic stirrer
  2. customwas purged with nitrogen
  3. filtrationthe resulting suspension was filtered
  4. dissolutionThe filter cake was dissolved in methylene chloride (20 mL)
  5. washthe solution was washed with 10% aqueous citric acid (10 mL), saturated aqueous sodium bicarbonate (10 mL), and water (10 mL)
  6. dry with materialdried over sodium sulfate
  7. customThe drying agent was removed by filtration
  8. customthe solvent was evaporated under reduced pressure
  9. customThe resulting residue was purified by flash chromatography

Quellen und Nachweise

ORD-Eintrag
ord-68addcbc6732439195f55e58b6e7b8b4
Quelldatensatz
uspto-grants-2012_08
Patentnummer
US08247550B2

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