Oxalyl chloride → (R)-4-(6-Benzyl-4,5-dimethyl-pyridazin-3-yl)-2-methyl-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl-5'-carboxylic acid methoxy-methyl-amide

HRID 447125Notes

Reaction equation

[CH2:1]([C:8]1[N:13]=[N:12][C:11]([N:14]2[CH2:19][CH2:18][N:17]([C:20]3[CH:25]=[N:24][C:23]([C:26](O)=[O:27])=[CH:22][N:21]=3)[C@H:16]([CH3:29])[CH2:15]2)=[C:10]([CH3:30])[C:9]=1[CH3:31])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(Cl)(=O)C(Cl)=O.C(N(C(C)C)CC)(C)C.Cl.[CH3:48][NH:49][O:50][CH3:51]>C(Cl)Cl.CN(C=O)C>[CH3:51][O:50][N:49]([CH3:48])[C:26]([C:23]1[N:24]=[CH:25][C:20]([N:17]2[CH2:18][CH2:19][N:14]([C:11]3[N:12]=[N:13][C:8]([CH2:1][C:2]4[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=4)=[C:9]([CH3:31])[C:10]=3[CH3:30])[CH2:15][C@H:16]2[CH3:29])=[N:21][CH:22]=1)=[O:27]

Participants

Conditions

Temperature: 0 °C

Procedure

(R)-4-(6-Benzyl-4,5-dimethyl-pyridazin-3-yl)-2-methyl-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl-5′-carboxylic acid (50 mg, 0.120 mmol) is dissolved in CH2Cl2 (300 μL). The mixture is cooled to 0° C. and oxalyl chloride (32 μL. 0.358 mmol) is added followed by DMF (3 drops). While stirring, the reaction is warmed to room temperature over 3 h. Diisopropylethylamine (209 μL, 1.2 mmol) is added dropwise followed by addition of N,O-dimethylhydroxylamine hydrochloride (14 mg, 0.144 mmol). Allow the reaction to stir for 16 h. Concentrate the crude mixture in vacuo. The residue is purified by flash chromatography on silica gel (MeOH/CH2Cl2) to afford the title compound (42 mg, 76%).

Workup

temperaturethe reaction is warmed to room temperature over 3 h
customthe reaction
stirringto stir for 16 h
concentrationConcentrate the crude mixture in vacuo
customThe residue is purified by flash chromatography on silica gel (MeOH/CH2Cl2)

Sources & evidence

ORD record: ord-a25e9b6ba0604ee395843233461fc92e
Source dataset: uspto-grants-2013_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08481542B2

Reaction notes

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