Dimethylformamide → HCID 68283666, compound

HRID 1527313Notes

Reaction equation

I[C:2]1[C:10]2[C:5](=[N:6][N:7]=[CH:8][CH:9]=2)[N:4]([CH2:11][C:12]([O:14]C)=[O:13])[N:3]=1.C(Cl)Cl.C[N:20]([CH:22]=[O:23])C>O.[C-]#N.[C-]#N.[Zn+2].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].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:22]([C:2]1[C:10]2[C:5](=[N:6][N:7]=[CH:8][CH:9]=2)[N:4]([CH2:11][C:12]([OH:14])=[O:13])[N:3]=1)(=[O:23])[NH2:20]

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of methyl 2-(3-iodo-1H-pyrazolo[3,4-c]pyridazin-1-yl)acetate (675 mg, 2.12 mmol) in DMF (7.5 mL) and water (1.5 mL) was added Zn(CN)2 (274 mg, 2.33 mmol), Pd2 dba3 (194 mg, 0.21 mmol) and PdCl2(dppf).CH2Cl2 adduct (173 mg, 0.21 mmol). The reaction mixture was stirred at 100° C. for 16 h. The resulting suspension was filtered and the filtrate was evaporated under vacuum. The residue was suspended in CH3CN/MeOH 1:1, the solid was filtered off and the filtrate was purified by preparative HPLC (Macherey Nagel, VP250/40, C18 Nucleosil 100-10, flow: 40 mL/min, eluent: 5-100% CH3CN/H2O/20 min, 100% CH3CN/2 min, CH3CN and H2O containing 0.1% TFA) to give the title compound after lyophilisation. MS (LC/MS): 222.1 [M+H]+; tR (HPLC conditions c): 1.34 min.

Workup

filtrationThe resulting suspension was filtered
customthe filtrate was evaporated under vacuum
filtrationthe solid was filtered off
customthe filtrate was purified by preparative HPLC (Macherey Nagel, VP250/40, C18 Nucleosil 100-10, flow: 40 mL/min, eluent: 5-100% CH3CN/H2O/20 min, 100% CH3CN/2 min, CH3CN and H2O containing 0.1% TFA)

Sources & evidence

ORD record: ord-cf1f7ed7f1454ae6aa95e116dd12de49
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09085555B2

Reaction notes

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