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Diisopropylethylamine → 5-(3-(1-(Cyclopropylsulfonylcarbamoyl)cyclopropylcarbamoyl)phenyl)-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamide

HRID 1025119
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Reaktionsgleichung

Reaktionsgleichung von HRID 1025119
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]3[CH:20]=[CH:19][C:18]([C:21]4[CH:22]=[C:23]([CH:27]=[CH:28][CH:29]=4)[C:24](O)=[O:25])=[CH:17][C:11]=3[C:12]=2[C:13](=[O:16])[NH:14][CH3:15])=[CH:4][CH:3]=1.Cl.[NH2:31][C:32]1([C:35]([NH:37][S:38]([CH:41]2[CH2:43][CH2:42]2)(=[O:40])=[O:39])=[O:36])[CH2:34][CH2:33]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CO.CN(C=O)C>[CH:41]1([S:38]([NH:37][C:35]([C:32]2([NH:31][C:24]([C:23]3[CH:22]=[C:21]([C:18]4[CH:19]=[CH:20][C:10]5[O:9][C:8]([C:5]6[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=6)=[C:12]([C:13]([NH:14][CH3:15])=[O:16])[C:11]=5[CH:17]=4)[CH:29]=[CH:28][CH:27]=3)=[O:25])[CH2:34][CH2:33]2)=[O:36])(=[O:40])=[O:39])[CH2:43][CH2:42]1
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Komponenten

7

Edukt 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 592754243-[2-(4-Fluorophenyl)-3-(methylcarbamoyl)-1-benzofuran-5-yl]benzoic acidHCID 672117341-amino-N-(cyclopropylsulfonyl)cyclopropanecarboxamide hydrochloride

Produkt 1

HCID 59275649
5-(3-(1-(Cyclopropylsulfonylcarbamoyl)cyclopropylcarbamoyl)phenyl)-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamide
Ausbeute 52 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittelHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

In a 7 mL scintillation vial were combined 3-(2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)benzoic acid (30 mg, 0.077 mmol), 1-amino-N-(cyclopropylsulfonyl)cyclopropanecarboxamide hydrochloride (20 mg, 0.083 mmol), and HATU (40 mg, 0.10 mmol). DMF (0.4 mL) and DIPEA (0.1 mL, 0.57 mmol) were added, the vial was capped, and the solution was stirred at r.t. for 45 min. The reaction was diluted with MeOH, filtered, purified by prep HPLC, and the collected fractions were concentrated on a speedvac to afford the title compound (23 mg, 52% yield) as a white powder. 1H NMR (500 MHz, DMSO-d6) δ ppm 8.99 (br. s., 1 H) 8.53 (q, J=4.78 Hz, 1 H) 8.25 (br. s., 1 H) 8.00 (dd, J=8.85, 5.49 Hz, 2 H) 7.93 (s, 1 H) 7.89 (t, J=7.78 Hz, 2 H) 7.72-7.83 (m, 2 H) 7.58 (t, J=7.48 Hz, 1 H) 7.40 (t, J=8.85 Hz, 2 H) 7.07 (br. s., 1 H) 2.89-2.98 (m, 1 H) 2.87 (d, J=4.58 Hz, 3 H) 1.35-1.56 (m, 2 H) 0.77-1.28 (m, 6 H). LC/MS was performed by using Shimadzu-VP instrument with UV detection at 220 nm and Waters Micromass. LC/MS method: solvent A=10% CH3CN/90% H2O/0.1% TFA, solvent B=90% CH3CN/10% H2O/0.1% TFA, start % B=0, final % B=100, gradient time=2 min, stop time=3 min, flow rate=4 ml/min, column: Sunfire C18 5 μm 4.6×50 mm; HPLC Rt=1.59 min, (ES+) m/z (MH+)=576. Analytical HPLC were performed using a Shimadzu-VP instrument with UV detection at 220 nm and 254 nm. Analytical HPLC method: solvent A=5% CH3OH/95% H2O/10 mM NH4HCO3, solvent B=95% CH3OH/5% H2O/10 mM NH4HCO3, start % B=10, final % B=100, gradient time=15 min, stop time=18 min, flow rate=1 ml/min. Column: Phenomenex Gemini C18, 4.6 mm, 3 μm, Rt=15.39 min, purity=100%; column: Waters Xbridge Phenyl 4.6×150 mm, 3.5 μm, Rt=14.50 min, purity=100%.

Aufarbeitung

  1. customthe vial was capped
  2. filtrationfiltered
  3. custompurified by prep HPLC
  4. concentrationthe collected fractions were concentrated on a speedvac

Quellen und Nachweise

ORD-Eintrag
ord-8f7e6008e5dc497a8abd559b014712cc
Quelldatensatz
uspto-grants-2014_05
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08722688B2

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