Diisobutylaluminum hydride → HCID 86696434, compound

HRID 870729Notes

Reaction equation

HRID 870729 reaction equation
Br[C:2]1[N:6]2[N:7]=[C:8]([NH:11][CH2:12][C@@H:13]3[CH2:17][CH2:16][CH2:15][N:14]3[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH:9]=[CH:10][C:5]2=[N:4][CH:3]=1.[CH2:25]([Zn]CC)[CH3:26].CC(C[AlH]CC(C)C)C>O1CCOCC1>[CH2:25]([C:2]1[N:6]2[N:7]=[C:8]([NH:11][CH2:12][C@@H:13]3[CH2:17][CH2:16][CH2:15][N:14]3[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH:9]=[CH:10][C:5]2=[N:4][CH:3]=1)[CH3:26]

Participants

5

Reactant 3

HCID 14487Diisobutylaluminum hydrideHCID 86696435HCID 86696435, compoundHCID 178418750HCID 178418750, compound

Product 1

HCID 86696434HCID 86696434, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of PdCl2dppf (25 mg, 0.03 mmol) and (S)-tert-butyl 2-(((3-bromoimidazo[1,2-b]pyridazin-6-yl)amino)methyl)pyrrolidine-1-carboxylate (100 mg, 0.2 mmol) in dioxane (2 mL) was added diethylzinc (0.24 ml, 1 M in hexane), DiBAL-H (0.008 mL, 1M in toluene) at room temperature. The reaction mixture was heated to 100° C. and stirred for 2 h. Filtered off celite, and concentrated the filtrate, purified by Prep HPLC (neutral) to give (S)-tert-butyl 2-(((3-ethylimidazo[1,2-b]pyridazin-6-yl)amino)methyl)pyrrolidine-1-carboxylate as oil. 1H NMR (400 MHz, METHANOL-d4) δ ppm 7.55 (d, J=9.60 Hz, 1H), 7.22 (s, 1H), 6.66 (d, J=9.60 Hz, 1H), 4.18 (br. s., 1H), 3.55 (br. s., 1H), 3.37-3.49 (m, 3H), 2.91 (q, J=7.49 Hz, 2H), 1.87-2.07 (m, 4H), 1.44 (br. s., 9H), 1.36 (t, J=7.45 Hz, 3H); LRMS (ESI) m/e 346.3 [(M+H)+, calcd for C18H28N6O2 346.4.

Workup

  1. filtrationFiltered off celite
  2. concentrationconcentrated the filtrate
  3. custompurified by Prep HPLC (neutral)

Sources & evidence

ORD record
ord-ba2f1e8b1a1647fe9204e87eda35d5e8
Source dataset
uspto-grants-2015_03
Patent number
US08969565B2

Reaction notes

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