Potassium Carbonate → HCID 86696448, compound

HRID 870740Notes

Reaction equation

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

Participants

Conditions

Temperature: 150 °C

Procedure

A mixture of (S)-2-[(3-bromo-imidazo[1,2-b]pyridazin-6-ylamino)-methyl]-pyrrolidine-1-carboxylic acid vinyl ester (125 mg, 0.34 mmol), (2-methoxyphenyl)boronic acid (67.2 mg, 0.44 mmol), K2CO3 (141 mg, 1.02 mmol) and dichlorobis(triphenylphosphine)palladium(II) (12 mg, 0.017 mmol) in MeCN/water (3.2 ml/0.8 ml) was heated in a microwave at 150° C. for 15 min. The reaction was repeated at 140° C. After removal of the water the reaction mixtures was combined and diluted with MeCN and filtered. The filtrate was subjected to preparative HPLC to give the titled compound (S)-2-[3-(2-Methoxy-phenyl)-imidazo[1,2-b]pyridazin-6-yl]-hexahydro-pyrrolo[1,2-c]imidazol-3-one (76.5 mg). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.39-1.51 (m, 1H) 1.89-2.02 (m, 1H) 2.05-2.18 (m, 2H) 3.18-3.26 (m, 1H) 3.72-3.96 (m, 6H) 4.09-4.16 (m, 1H) 7.04-7.13 (m, 2H) 7.35-7.42 (m, 1H) 7.90-7.96 (m, 1H) 8.03-8.10 (m, 2H) 8.40 (dd, J=9.85, 2.78 Hz, 1H). LRMS (ESI) m/z 350.2 [(M+H)]+, calc'd for C19H19N5O2: 349.4.

Workup

customwas repeated at 140° C
customAfter removal of the water
customthe reaction mixtures
filtrationfiltered

Sources & evidence

ORD record: ord-7d75cb66a82f4ad7bcf8d99af93a6bad
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08969565B2

Reaction notes

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