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

HRID 521584
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 521584
[S: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>[CH:10]([NH:12][CH2:13][CH2:14][CH2:15][N:16]1[C:25]([S:26][C:27]2[C:28]([C:2]3[S:1][CH:5]=[CH:4][CH:3]=3)=[CH:29][C:30]3[O:35][CH2:34][O:33][C:31]=3[CH:32]=2)=[N:24][C:18]2[C:17]1=[N:22][CH:21]=[N:20][C:19]=2[NH2:23])([CH3:11])[CH3:9]
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

7

Edukt 4

HCID 6228DimethylformamideHCID 516892Sodium BicarbonateHCID 27339602-Thiopheneboronic acidHCID 9549213Zelavespib

Produkt 1

HCID 671171149-(3-(isopropylamino)propyl)-8-(6-(thiophen-2-yl)benzo[d][1,3]dioxol-5-ylthio)-9H-purin-6-amineAusbeute 45,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418476
HCID 178418476, Verbindung
Katalysator
HCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

2-Thienylboronic acid (11.2 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 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 12.4 mg (45%) of DZ2-395. 1H NMR (500 MHz, CDCl3/MeOH-d4) δ 8.17 (s, 1H), 7.33 (dd, J=1.4, 4.9 Hz, 1H), 7.07 (s, 1H), 7.04 (s, 1H), 7.00-7.02 (m, 2H), 6.09 (s, 2H), 4.12 (t, J=6.6 Hz, 2H), 2.95 (septet, J=6.6 Hz, 1H), 2.62 (t, J=6.8 Hz, 2H), 2.00 (m, 2H), 1.19 (d, J=6.6 Hz, 6H); 13C NMR (125 MHz, CDCl3/MeOH-d4) δ 154.2, 152.0, 151.1, 149.4, 148.8, 148.4, 140.5, 132.9, 127.8, 126.9, 126.3, 119.2, 119.0, 114.6, 111.8, 102.3, 49.6, 42.5, 40.6, 27.8, 20.7; HRMS (ESI) m/z [M+H]+ calcd. for C22H25N6O2S2, 469.1480; found. 469.1461; HPLC: method A Rt=6.38, method B Rt=7.18.

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)

Quellen und Nachweise

ORD-Eintrag
ord-4ad86d7935b34b68be08ba0e30cb4da4
Quelldatensatz
uspto-grants-2016_05
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US09328114B2

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