Tetrahydrofuran → tert-Butyl 4-(5-(2-(hydroxymethyl)-8-morpholinoimidazo[1,2-b]pyridazin-3-yl)pyridin-2-yl)piperazine-1-carboxylate

HRID 718597Notes

Reaction equation

HRID 718597 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[N:19]=[CH:18][C:17]([C:20]3[N:24]4[N:25]=[CH:26][CH:27]=[C:28]([N:29]5[CH2:34][CH2:33][O:32][CH2:31][CH2:30]5)[C:23]4=[N:22][C:21]=3[C:35](OCC)=[O:36])=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[H-].[H-].[H-].[Li+].[Al+3].C1COCC1>>[OH:36][CH2:35][C:21]1[N:22]=[C:23]2[C:28]([N:29]3[CH2:30][CH2:31][O:32][CH2:33][CH2:34]3)=[CH:27][CH:26]=[N:25][N:24]2[C:20]=1[C:17]1[CH:16]=[CH:15][C:14]([N:11]2[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:9][CH2:10]2)=[N:19][CH:18]=1

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 21226445Aluminium lithium hydrideHCID 117728679Ethyl 3-(6-(4-(tert-butoxycarbonyl)piperazin-1-yl)pyridin-3-yl)-8-morpholinoimidazo[1,2-b]pyridazine-2-carboxylate

Product 1

HCID 117732471tert-Butyl 4-(5-(2-(hydroxymethyl)-8-morpholinoimidazo[1,2-b]pyridazin-3-yl)pyridin-2-yl)piperazine-1-carboxylate

Conditions

Temperature
0 °C

Procedure

Compound 20b (2.07 g, 3.85 mmol) was placed in a 100 mL round bottom flask equipped with a stir bar and then the flask was evacuated and backflushed with argon. Dry THF (40 mL) was added via syringe and then the solution was cooled to 0° C. in an ice bath. 1 M LiAlH4 in THF (3.85 mL, 3.85 mmol) was added via syringe and then the ice bath was removed and the reaction was allowed to warm to rt. The reaction was stirred at rt for 1 h and then poured into saturated NH4Cl solution (100 mL). The aqueous mixture was extracted with EtOAc (4×50 mL) and then the combined organic extracts were dried over MgSO4 and filtered. The solvent was removed under reduced pressure to afford compound 21a. 1H-NMR (400 MHz, CDCl3) δ (ppm): 8.48 (d, J=2.2 Hz, 1H), 8.01 (d, J=5.4 Hz, 1H), 7.90 (dd, J=8.8, 2.4 Hz, 1H), 6.77 (d, J=9.0 Hz, 1H), 6.09 (d, J=5.6 Hz, 1H), 4.83 (s, 2H), 3.93 (d, J=3.4 Hz, 8H), 3.51-3.66 (m, 8H), 1.50 (s, 9H). Mass Spectrum (LCMS, ESI pos.) Calcd. For C25H33N7O4: 496.3 (M+H). Found: 496.3.

Workup

  1. customequipped with a stir bar
  2. customthe flask was evacuated
  3. additionDry THF (40 mL) was added via syringe
  4. customthe ice bath was removed
  5. temperatureto warm to rt
  6. additionpoured into saturated NH4Cl solution (100 mL)
  7. extractionThe aqueous mixture was extracted with EtOAc (4×50 mL)
  8. dry with materialthe combined organic extracts were dried over MgSO4
  9. filtrationfiltered
  10. customThe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-afca6c32d5104a0c8d6cad88ed5499bb
Source dataset
uspto-grants-2015_11
Patent number
US09193736B2

Reaction notes

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