Potassium Carbonate → {(S)-1-[3-(2-Methoxy-pyridin-3-yl)-imidazo[1,2-b]pyridazin-6-yl]-pyrrolidin-3-yl}-methyl-carbamic acid isopropyl ester

HRID 870773Notes

Reaction equation

HRID 870773 reaction equation
[CH:1]([O:4][C:5](=[O:23])[N:6]([C@H:8]1[CH2:12][CH2:11][N:10]([C:13]2[CH:14]=[CH:15][C:16]3[N:17]([C:19](Br)=[CH:20][N:21]=3)[N:18]=2)[CH2:9]1)[CH3:7])([CH3:3])[CH3:2].[CH3:24][O:25][C:26]1[C:31](B(O)O)=[CH:30][CH:29]=[CH:28][N:27]=1.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>[CH:1]([O:4][C:5](=[O:23])[N:6]([C@H:8]1[CH2:12][CH2:11][N:10]([C:13]2[CH:14]=[CH:15][C:16]3[N:17]([C:19]([C:31]4[C:26]([O:25][CH3:24])=[N:27][CH:28]=[CH:29][CH:30]=4)=[CH:20][N:21]=3)[N:18]=2)[CH2:9]1)[CH3:7])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 2762709(2-Methoxypyridin-3-yl)boronic acidHCID 86696483(S)-isopropyl (1-(3-bromoimidazo[1,2-b]pyridazin-6-yl)pyrrolidin-3-yl)(methyl)carbamate

Product 1

HCID 71721711{(S)-1-[3-(2-Methoxy-pyridin-3-yl)-imidazo[1,2-b]pyridazin-6-yl]-pyrrolidin-3-yl}-methyl-carbamic acid isopropyl esterYield 87.4%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
150 °C

Procedure

A mixture of [(S)-1-(3-bromo-imidazo[1,2-b]pyridazin-6-yl)-pyrrolidin-3-yl]-methyl-carbamic acid isopropyl ester (88 mg, 0.23 mmol), 2-methoxypyridine-3-boronic acid (46 mg, 0.3 mmol), K2CO3 (95 mg, 0.69 mmol) and dichlorobis(triphenylphosphine)palladium(II) (8.4 mg, 0.012 mmol) in MeCN/water (3.2 ml/0.8 ml) was heated in a microwave at 150° C. for 15 min. The water layer was removed and the organic layer was diluted with MeCN and filtered. The filtrate was subjected to preparative HPLC to give the titled compound (82.5 mg). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.29 (d, J=6.06 Hz, 6H) 2.13-2.32 (m, 2H) 2.89 (s, 3H) 3.43 (dd, J=10.48, 6.95 Hz, 1H) 3.48-3.56 (m, 1H) 3.69-3.76 (m, 2H) 4.09 (s, 3H) 4.99 (dt, J=12.38, 6.19 Hz, 2H) 6.62 (d, J=9.85 Hz, 1H) 7.04 (dd, J=7.45, 4.93 Hz, 1H) 7.79 (d, J=9.85 Hz, 1H) 8.13-8.19 (m, 2H) 8.86 (dd, J=7.71, 1.64 Hz, 1H). LRMS (ESI) m/z 411.2 [(M+H)]+, calc'd for C21H26N6O3: 410.48.

Workup

  1. customThe water layer was removed
  2. additionthe organic layer was diluted with MeCN
  3. filtrationfiltered

Sources & evidence

ORD record
ord-ea4420a88f044e71a89789c5f110135d
Source dataset
uspto-grants-2015_03
Patent number
US08969565B2

Reaction notes

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