Potassium Carbonate → Isopropyl-carbamic acid 4-(6-butylamino-imidazo[1,2-b]pyridazin-3-yl)-benzyl ester

HRID 870701Notes

Reaction equation

HRID 870701 reaction equation
Br[C:2]1[N:6]2[N:7]=[C:8]([NH:11][CH2:12][CH2:13][CH2:14][CH3:15])[CH:9]=[CH:10][C:5]2=[N:4][CH:3]=1.CC1(C)C(C)(C)OB([C:24]2[CH:37]=[CH:36][C:27]([CH2:28][O:29][C:30](=[O:35])[NH:31][CH:32]([CH3:34])[CH3:33])=[CH:26][CH:25]=2)O1.C([O-])([O-])=O.[K+].[K+]>CC#N.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH2:12]([NH:11][C:8]1[CH:9]=[CH:10][C:5]2[N:6]([C:2]([C:24]3[CH:37]=[CH:36][C:27]([CH2:28][O:29][C:30](=[O:35])[NH:31][CH:32]([CH3:33])[CH3:34])=[CH:26][CH:25]=3)=[CH:3][N:4]=2)[N:7]=1)[CH2:13][CH2:14][CH3:15]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 866963223-Bromo-6-(butylamino)imidazo[1,2-b]pyridazineHCID 866964024-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl isopropylcarbamate

Product 1

HCID 86696403Isopropyl-carbamic acid 4-(6-butylamino-imidazo[1,2-b]pyridazin-3-yl)-benzyl esterYield 138%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 18373917Acetonitrile--water (1/1)Solvent

Conditions

Temperature
140 °C

Procedure

A mixture of (3-bromo-imidazo[1,2-b]pyridazin-6-yl)-butyl-amine (50 mg, 0.19 mmol), isopropyl-carbamic acid 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzyl ester (from part A, ˜0.5 mmol), K2CO3 (77 mg, 0.56 mmol) and dichlorobis(triphenylphosphine)palladium(II) (6.5 mg, 0.01 mmol) in MeCN/water (2 ml/0.5 ml) was heated in a microwave at 140° C. for 10 min. The reaction was repeated with another half of the bronic ester from Part A. The two reactions were combined for purification. The water layer was removed and the reaction mixture was diluted with MeCN (3 ml) and filtered. The filtrate was subjected to preparative HPLC to give the titled compound (100 mg). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.00 (t, J=7.39 Hz, 3H) 1.19 (d, J=6.62 Hz, 6H) 1.43-1.52 (m, 2H) 1.66-1.73 (m, 2H) 3.41 (td, J=7.06, 5.73 Hz, 2H) 3.87 (d, J=6.84 Hz, 1H) 4.49 (t, J=5.29 Hz, 1H) 5.14 (m, 1H) 6.45 (d, J=9.70 Hz, 1H) 7.46 (d, J=8.16 Hz, 2H) 7.66 (d, J=9.48 Hz, 1H) 7.81 (s, 1H) 8.14 (d, J=8.38 Hz, 2H). LRMS (ESI) m/z 382.2 [(M+H)]+, calc'd for C21H27N5O2: 381.48.

Workup

  1. customThe two reactions were combined for purification
  2. customThe water layer was removed
  3. additionthe reaction mixture was diluted with MeCN (3 ml)
  4. filtrationfiltered

Sources & evidence

ORD record
ord-90593c318bb5400face4a1f918a8a648
Source dataset
uspto-grants-2015_03
Patent number
US08969565B2

Reaction notes

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