N,N'-Dimethylethylenediamine → HCID 86696424, compound

HRID 870720Notes

Reaction equation

HRID 870720 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][CH:21]([CH3:23])[CH3:22])=[O:19])[CH:9]=[CH:10][C:5]2=[N:4][CH:3]=1.[C-]#N.[Na+].[CH3:27][NH:28]CCNC>C1(C)C=CC=CC=1.[Cu]I>[C:27]([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][CH:21]([CH3:23])[CH3:22])=[O:19])[CH:9]=[CH:10][C:5]2=[N:4][CH:3]=1)#[N:28]

Participants

6

Reactant 3

HCID 8070N,N'-DimethylethylenediamineHCID 8929Sodium CyanideHCID 86696425HCID 86696425, compound

Product 1

HCID 86696424HCID 86696424, compoundYield 25%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 1140TolueneSolvent

Procedure

A solution of (S)-iso-propyl 2-(((3-bromoimidazo[1,2-b]pyridazin-6-yl)amino)methyl)pyrrolidine-1-carboxylate (300 mg, 0.79 mmol), NaCN (46 mg, 0.94 mmol), CuI (15 mg, 0.08 mmol), KI (27 mg, 0.16 mmol) and N1,N2-dimethylethane-1,2-diamine (0.085 mL, 0.79 mmol) in toluene (0.8 mL) was stirred at 110° C. for 12 h. The reaction was cooled, concentrated, taken up with EtOAc and water, extracted and dried organic layer with MgSO4. The organic layer was concentrated and purified by ISCO (0-5% MeOH/DCM), then following PREP HPLC (neutral) to give (S)-isopropyl 2-(((3-cyanoimidazo[1,2-b]pyridazin-6-yl)amino)methyl)pyrrolidine-1-carboxylate (63 mg, 25% yield). 1H NMR (400 MHz, METHANOL-d4) δ ppm 8.00 (s, 1H), 7.72 (d, J=9.85 Hz, 1H), 6.91 (d, J=9.85 Hz, 1H), 4.20 (m, 1H), 3.38-3.61 (m, 4H), 1.97-2.05 (m, 4H), 1.16-1.25 (m, 6H); LRMS (ESI) m/e 329.2 [(M+H)+, calcd for C16H21N6O2 329.4].

Workup

  1. temperatureThe reaction was cooled
  2. concentrationconcentrated
  3. extractionextracted
  4. concentrationThe organic layer was concentrated
  5. custompurified by ISCO (0-5% MeOH/DCM)

Sources & evidence

ORD record
ord-90684c4ce0a94042a87ba2e358b23aa0
Source dataset
uspto-grants-2015_03
Patent number
US08969565B2

Reaction notes

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