2-(1-((7-Morpholino-5-(tributylstannyl)thiazolo[5,4-d]pyrimidin-2-yl)methyl)piperidin-4-yl)propan-2-ol → 2-(1-((5-(1H-indazol-3-yl)-7-morpholinothiazolo[5,4-d]pyrimidin-2-yl)methyl)piperidin-4-yl)propan-2-ol

HRID 1922968Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1922968
[O:1]1[CH2:6][CH2:5][N:4]([C:7]2[C:8]3[N:28]=[C:27]([CH2:29][N:30]4[CH2:35][CH2:34][CH:33]([C:36]([OH:39])([CH3:38])[CH3:37])[CH2:32][CH2:31]4)[S:26][C:9]=3[N:10]=[C:11]([Sn](CCCC)(CCCC)CCCC)[N:12]=2)[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:4]3[CH2:5][CH2:6][O:1][CH2:2][CH2:3]3)[C:8]3[N:28]=[C:27]([CH2:29][N:30]4[CH2:35][CH2:34][CH:33]([C:36]([OH:39])([CH3:38])[CH3:37])[CH2:32][CH2:31]4)[S:26][C:9]=3[N:10]=2)=[N:42]1

Komponenten

6

Edukt 2

HCID 596055632-(1-((7-Morpholino-5-(tributylstannyl)thiazolo[5,4-d]pyrimidin-2-yl)methyl)piperidin-4-yl)propan-2-olHCID 178506566HCID 178506566, Verbindung

Produkt 1

HCID 498322742-(1-((5-(1H-indazol-3-yl)-7-morpholinothiazolo[5,4-d]pyrimidin-2-yl)methyl)piperidin-4-yl)propan-2-olAusbeute 28 %

Reagenzien, Katalysatoren, Lösungsmittel 3

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

Versuchsvorschrift

A mixture of 2-(1-((7-morpholino-5-(tributylstannyl)thiazolo[5,4-d]pyrimidin-2-yl)methyl)piperidin-4-yl)propan-2-ol (0.211 g, 0.32 mmol), 3-iodo-1H-indazole (0.116 g, 0.48 mmol), copper(I) 2-thiophene carboxylate (0.012 g, 0.064 mmol) and Pd(PPh3)4 (0.037 g, 0.032 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 resultant residue was purified by flash chromatography (Si—PPC, MEOH:DCM, gradient 0:100 to 10:90) to give 209 as a yellow solid (0.043 g, 28%). LCMS (Method G): RT=7.71 min, [M+H]+ 494.3. 1H NMR (400 MHz, DMSO-d): δ 13.45 (s, 1 H); 8.48 (d, J=8.3 Hz, 1 H); 7.61 (d, J=8.3 Hz, 1 H); 7.41 (t, J=7.6 Hz, 1 H); 7.26 (t, J=7.6 Hz, 1 H); 4.37 (m, 4 H); 3.88 (s, 2 H); 3.82 (t, J=4.6 Hz, 4 H); 3.02 (d, J=11.0 Hz, 2 H); 2.12 (t, J=11.0 Hz, 2 H); 1.74-1.69 (m, 2 H); 1.36-1.28 (m, 2 H); 1.26-1.23 (m, 2 H); 1.06 (s, 6 H)

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 resultant residue was purified by flash chromatography (Si—PPC, MEOH:DCM, gradient 0:100 to 10:90)

Quellen und Nachweise

ORD-Eintrag
ord-aad33ae98a904fa1a644a0dc244527c6
Quelldatensatz
uspto-grants-2012_05
Patentnummer
US08173650B2

Notizen zur Reaktion

Wird geladen…