Dichloromethane → tert-Butyl(2-((3-(4-carbamoylphenyl)imidazo[1,2-b]pyridazin-6-yl)amino)ethyl)(methyl)carbamate

HRID 870703Notes

Reaction equation

HRID 870703 reaction equation
[C:1]([O:5][C:6](=[O:22])[N:7]([CH2:9][CH2:10][NH:11][C:12]1[CH:13]=[CH:14][C:15]2[N:16]([C:18](Br)=[CH:19][N:20]=2)[N:17]=1)[CH3:8])([CH3:4])([CH3:3])[CH3:2].[C:23]([C:26]1[CH:31]=[CH:30][C:29](B(O)O)=[CH:28][CH:27]=1)(=[O:25])[NH2:24].O.[O-]P([O-])([O-])=O.[K+].[K+].[K+].ClCCl>O.COCCOC.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(OCC)(=O)C.CCCCCCC>[C:1]([O:5][C:6](=[O:22])[N:7]([CH2:9][CH2:10][NH:11][C:12]1[CH:13]=[CH:14][C:15]2[N:16]([C:18]([C:29]3[CH:30]=[CH:31][C:26]([C:23](=[O:25])[NH2:24])=[CH:27][CH:28]=3)=[CH:19][N:20]=2)[N:17]=1)[CH3:8])([CH3:4])([CH3:3])[CH3:2]

Participants

9

Reactant 4

HCID 6344DichloromethaneHCID 27378114-Aminocarbonylphenylboronic acidHCID 22031701Potassium phosphate, tribasic, monohydrateHCID 86696401[2-(3-Bromo-imidazo[1,2-b]pyridazin-6-ylamino)-ethyl]-methyl-carbamic acid tert-butyl ester

Product 1

HCID 86696405tert-Butyl(2-((3-(4-carbamoylphenyl)imidazo[1,2-b]pyridazin-6-yl)amino)ethyl)(methyl)carbamate

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolventHCID 21899848Ethylacetate heptaneSolvent

Procedure

{2-[3-(4-Carbamoyl-phenyl)-imidazo[1,2-b]pyridazin-6-ylamino]-ethyl}-methyl-carbamic acid tert-butyl ester was prepared similarly to the procedure for example 5.6.60 from [2-(3-bromo-imidazo[1,2-b]pyridazin-6-ylamino)-ethyl]-methyl-carbamic acid tert-butyl ester (367.4 mg, 1.0 mmol), (4-carbamoylphenyl)boronic acid [123088-59-5] (196.7 mg, 1.2 mmol), potassium phosphate tribasic monohydrate [27176-10-9] (418.4 mg, 1.8 mmol), and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane [95464-05-4] (82.1 mg, 0.1 mmol) in 30% (v/v) water in 1,2-dimethoxyethane (25 mL) at 85° C. for 17 h. White powder from ethyl acetate/heptane, mp. 190-191° C. (dec.). 1H NMR (400 MHz, DMSO-d6) δ ppm (rotamers present) 1.15 (br. s., 5H) 1.28 (br. s., 1H) 1.38 (br. s., 3H) 2.85 (br. s., 3H) 3.32 (br. s., 1H) 3.54 (br. s., 1H) 6.73 (d, J=9.35 Hz, 1H) 7.27 (br. s., 1H) 7.34 (br. s., 1H) 7.79 (d, J=9.60 Hz, 1H) 7.94-8.03 (m, 4H) 8.28 (d, J=8.08 Hz, 2H). LRMS (ESI) m/z 411.2 [(M+H)]+, calc'd for C21H26N6O3: 410.48.

Sources & evidence

ORD record
ord-2330b8e4ad6742e6bc76dabfda7c0ac9
Source dataset
uspto-grants-2015_03
Patent number
US08969565B2

Reaction notes

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