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Dimethylformamide → 8-(6-(furan-2-yl)benzo[d][1,3]dioxol-5-ylthio)-9-(3-(isopropylamino)propyl)-9H-purin-6-amine

HRID 521585
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 521585
[O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1B(O)O.[CH3:9][CH:10]([NH:12][CH2:13][CH2:14][CH2:15][N:16]1[C:25]([S:26][C:27]2[CH:32]=[C:31]3[O:33][CH2:34][O:35][C:30]3=[CH:29][C:28]=2I)=[N:24][C:18]2[C:19]([NH2:23])=[N:20][CH:21]=[N:22][C:17]1=2)[CH3:11].C([O-])(O)=O.[Na+].CN(C=O)C>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:28]1[C:27]([S:26][C:25]2[N:16]([CH2:15][CH2:14][CH2:13][NH:12][CH:10]([CH3:11])[CH3:9])[C:17]3[C:18]([N:24]=2)=[C:19]([NH2:23])[N:20]=[CH:21][N:22]=3)=[CH:32][C:31]2[O:33][CH2:34][O:35][C:30]=2[CH:29]=1
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

7

Edukt 4

HCID 6228DimethylformamideHCID 516892Sodium BicarbonateHCID 2734357Furan-2-boronic acidHCID 9549213Zelavespib

Produkt 1

HCID 671156058-(6-(furan-2-yl)benzo[d][1,3]dioxol-5-ylthio)-9-(3-(isopropylamino)propyl)-9H-purin-6-amine

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418476
HCID 178418476, Verbindung
Katalysator
HCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

2-Furanylboronic acid (9.8 mg, 0.0877 mmol) was added to PU-H71 (30 mg, 0.0585 mmol) and NaHCO3 (14.7 mg, 0.1755 mmol). DMF (1 mL) was added and the reaction mixture was evacuated and back filled with nitrogen. This was repeated four times then nitrogen was bubbled through the reaction mixture for 10 minutes. Then H2O (0.1 mL) and Pd(PPh3)2Cl2 (4 mg, 0.00584 mmol) were added and the reaction mixture was heated under nitrogen at 90° C. for 3.5 h. Solvent was removed under reduced pressure and the resulting residue was purified by preparatory TLC (CH2Cl2:MeOH—NH3 (7N), 12.5:1) to give 19.1 mg (72%) of DZ3-4. 1H NMR (500 MHz, CDCl3/MeOH-d4) δ 8.18 (s, 1H), 7.49 (d, J=1.8 Hz, 1H), 7.25 (s, 1H), 6.96 (s, 1H), 6.71 (d, J=3.3 Hz, 1H), 6.47 (dd, J=1.8, 3.2 Hz, 1H), 6.06 (s, 2H), 4.20 (t, J=7.0 Hz, 2H), 2.87 (m, 1H), 2.61 (t, J=6.9 Hz, 2H), 2.00 (m, 2H), 1.14 (d, J=6.3 Hz, 6H); 13C NMR (125 MHz, CDCl3/MeOH-d4) δ 154.3, 152.2, 151.2, 150.9, 149.5, 148.14, 148.08, 142.4, 129.0, 119.2, 117.5, 114.5, 111.5, 110.0, 109.0, 102.3, 42.8, 41.0, 28.5, 21.2; HRMS (ESI) m/z [M+H]+ calcd. for C22H25N6O3S, 453.1709; found. 453.1705; HPLC: method A Rt=6.23, method B Rt=6.82.

Aufarbeitung

  1. customthe reaction mixture was evacuated
  2. additionback filled with nitrogen
  3. customnitrogen was bubbled through the reaction mixture for 10 minutes
  4. customSolvent was removed under reduced pressure
  5. customthe resulting residue was purified by preparatory TLC (CH2Cl2:MeOH—NH3 (7N), 12.5:1)
  6. customto give 19.1 mg (72%) of DZ3-4

Quellen und Nachweise

ORD-Eintrag
ord-b991503ff85f4a31adfc9759ea95ea77
Quelldatensatz
uspto-grants-2016_05
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US09328114B2

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