5-Bromo-2-methylimidazo[1,2-a]pyridine → 2-(1-((9-methyl-2-(2-methylimidazo[1,2-a]pyridin-5-yl)-6-morpholino-9H-purin-8-yl)methyl)piperidin-4-yl)propan-2-ol

HRID 1923303

Reaktionsgleichung

Reaktionsgleichung von HRID 1923303
[CH3:1][N:2]1[C:10]([CH2:11][N:12]2[CH2:17][CH2:16][CH:15]([C:18]([OH:21])([CH3:20])[CH3:19])[CH2:14][CH2:13]2)=[N:9][C:8]2[C:3]1=[N:4][C:5]([Sn](CCCC)(CCCC)CCCC)=[N:6][C:7]=2[N:22]1[CH2:27][CH2:26][O:25][CH2:24][CH2:23]1.Br[C:42]1[N:47]2[CH:48]=[C:49]([CH3:51])[N:50]=[C:46]2[CH:45]=[CH:44][CH:43]=1>O1CCOCC1.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.S1C=CC=C1C([O-])=O.[Cu+]>[CH3:1][N:2]1[C:10]([CH2:11][N:12]2[CH2:13][CH2:14][CH:15]([C:18]([OH:21])([CH3:19])[CH3:20])[CH2:16][CH2:17]2)=[N:9][C:8]2[C:3]1=[N:4][C:5]([C:42]1[N:47]3[CH:48]=[C:49]([CH3:51])[N:50]=[C:46]3[CH:45]=[CH:44][CH:43]=1)=[N:6][C:7]=2[N:22]1[CH2:27][CH2:26][O:25][CH2:24][CH2:23]1

Komponenten

6

Edukt 2

HCID 126377285-Bromo-2-methylimidazo[1,2-a]pyridineHCID 596055362-(1-((9-Methyl-6-morpholino-2-(tributylstannyl)-9H-purin-8-yl)methyl)piperidin-4-yl)propan-2-ol

Produkt 1

HCID 596058632-(1-((9-methyl-2-(2-methylimidazo[1,2-a]pyridin-5-yl)-6-morpholino-9H-purin-8-yl)methyl)piperidin-4-yl)propan-2-olAusbeute 31,3 %

Reagenzien, Katalysatoren, Lösungsmittel 3

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

Reaktionsbedingungen

Temperatur
150 °C

Versuchsvorschrift

A mixture of 2-[1-(9-methyl-6-morpholin-4-yl-2-(tributylstannanyl)-9H-purin-8-ylmethyl)-piperidin-4-yl]propan-2-ol (127 mg, 0.19 mmol), 5-bromo-2-methyl-imidazo[1,2-a]pyridine (48 mg, 0.23 mmol), Pd(PPh3)4(22 mg, 0.02 mmol) and copper(I) thiophene-2-carboxylate (7 mg, 0.04 mmol) in dioxane (2 mL) was purged with argon gas then heated at 150° C., for 20 min, in a microwave reactor. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge (10 g). The cartridge was washed with MeOH then the desired product eluted with 2 M NH3 in MeOH. The resulting residue was purified by flash chromatography (Si—PPC, MeOH:DCM, gradient 0:100 to 0:100) 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 692 as a pale yellow solid (30 mg, 31%). LCMS (Method E) RT 4.77 min; [M+H]+ 505. 1H NMR (400 MHz, CHCl3-d): δ 8.98 (s, 1 H); 7.91 (dd, J=7.2, 1.2 Hz, 1 H); 7.66 (d, J=8.8 Hz, 1 H); 7.30-7.25 (m, 1 H); 4.38 (s, 4 H); 3.96 (s, 3 H); 3.89 (t, J=4.7 Hz, 4 H); 3.75 (s, 2 H); 2.96 (d, J=11.0 Hz, 2 H); 2.54 (s, 3 H); 2.12 (t, J=11.0 Hz, 2 H); 1.81-1.71 (m, 1 H); 1.45-1.23 (m, 4 H); 1.19 (s, 6 H)

Aufarbeitung

  1. customwas purged with argon gas
  2. washThe cartridge was washed with MeOH
  3. washthe desired product eluted with 2 M NH3 in MeOH
  4. customThe resulting residue was purified by flash chromatography (Si—PPC, MeOH:DCM, gradient 0:100 to 0:100)

Quellen und Nachweise

ORD-Eintrag
ord-1f2f8b595e484a16878f1c61c68c58b7
Quelldatensatz
uspto-grants-2012_05
Patentnummer
US08173650B2

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