7-Morpholin-4-yl-2-(3-morpholin-4-ylazetidin-1-ylmethyl)-5-(tributylstannanyl)thiazolo[5,4-d]pyrimidine → 4-(5-(1H-indazol-3-yl)-2-((3-morpholinoazetidin-1-yl)methyl)thiazolo[5,4-d]pyrimidin-7-yl)morpholine

HRID 1922946

Reaktionsgleichung

Reaktionsgleichung von HRID 1922946
[N:1]1([C:7]2[C:8]3[N:28]=[C:27]([CH2:29][N:30]4[CH2:33][CH:32]([N:34]5[CH2:39][CH2:38][O:37][CH2:36][CH2:35]5)[CH2:31]4)[S:26][C:9]=3[N:10]=[C:11]([Sn](CCCC)(CCCC)CCCC)[N:12]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.I[C:41]1[C:49]2[C:44](=[CH:45][CH:46]=[CH:47][CH:48]=2)[NH:43][N:42]=1>O1CCOCC1.S1C=CC=C1C([O-])=O.[Cu+].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>[NH:43]1[C:44]2[C:49](=[CH:48][CH:47]=[CH:46][CH:45]=2)[C:41]([C:11]2[N:12]=[C:7]([N:1]3[CH2:6][CH2:5][O:4][CH2:3][CH2:2]3)[C:8]3[N:28]=[C:27]([CH2:29][N:30]4[CH2:31][CH:32]([N:34]5[CH2:39][CH2:38][O:37][CH2:36][CH2:35]5)[CH2:33]4)[S:26][C:9]=3[N:10]=2)=[N:42]1

Komponenten

6

Edukt 2

HCID 596060507-Morpholin-4-yl-2-(3-morpholin-4-ylazetidin-1-ylmethyl)-5-(tributylstannanyl)thiazolo[5,4-d]pyrimidineHCID 178506566HCID 178506566, Verbindung

Produkt 1

HCID 674924374-(5-(1H-indazol-3-yl)-2-((3-morpholinoazetidin-1-yl)methyl)thiazolo[5,4-d]pyrimidin-7-yl)morpholineAusbeute 20 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 11194830Cuprous 2-thiophenecarboxylateKatalysatorHCID 178418397HCID 178418397, VerbindungKatalysatorHCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

A mixture of 7-morpholin-4-yl-2-(3-morpholin-4-ylazetidin-1-ylmethyl)-5-(tributylstannanyl)thiazolo[5,4-d]pyrimidine (0.25 g, 0.37 mmol), 3-iodo-1H-indazole (0.2 g, 0.82 mmol), copper(I) 2-thiophene carboxylate (0.030 g, 0.150 mmol) and Pd(PPh3)4 (0.088 g, 0.075 mmol) in dioxane (3 mL) was subjected to microwave irradiation at 150° C. for 90 min. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge. The cartridge was washed with MeOH and the desired product was eluted using 2 M NH3 in MeOH. The eluent was concentrated in vacuo and the residue was purified by flash chromatography (Si—PPC, MEOH:DCM, gradient 0:100 to 20:80) followed by reverse phase HPLC (Phenomenex Gemini 5u C18, 20 mM triethylamine in water on a gradient of acetonitrile 95:5 to 2:98) to give 182 as an off-white solid (0.036 g, 20%). LCMS (Method G): RT=7.40 min, [M+H]+ 493.3. 1H NMR (CDCl3, 400 MHz) δ 8.58 (d, J=8.2 Hz, 1 H); 7.55 (t, J=8.2 Hz, 1 H); 7.46-7.41 (m, 1 H); 7.34-7.29 (m, 1 H); 4.48-4.33 (m, 4 H); 4.02 (s, 2 H); 3.92 (t, J=4.6 Hz, 4 H); 3.73 (t, J=4.6 Hz, 4 H); 3.70-3.66 (m, 2 H); 3.18-3.09 (m, 3 H); 2.40-2.35 (m, 4H)

Aufarbeitung

  1. customirradiation at 150° C. for 90 min
  2. washThe cartridge was washed with MeOH
  3. washthe desired product was eluted
  4. concentrationThe eluent was concentrated in vacuo
  5. customthe residue was purified by flash chromatography (Si—PPC, MEOH:DCM, gradient 0:100 to 20:80)

Quellen und Nachweise

ORD-Eintrag
ord-345264b0a79045dc8240c8709505b6b2
Quelldatensatz
uspto-grants-2012_05
Patentnummer
US08173650B2

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