(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 → 1-[(R)-4-(6-Benzyl-4,5-dimethyl-pyridazin-3-yl)-2-methyl-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl-5'-yl]-ethanone

HRID 1480005Notes

Reaction equation

CON(C)[C:4]([C:6]1[N:7]=[CH:8][C:9]([N:12]2[CH2:17][CH2:16][N:15]([C:18]3[N:19]=[N:20][C:21]([CH2:26][C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)=[C:22]([CH3:25])[C:23]=3[CH3:24])[CH2:14][C@H:13]2[CH3:33])=[N:10][CH:11]=1)=[O:5].[CH3:35][Mg]I>C1COCC1>[CH2:26]([C:21]1[N:20]=[N:19][C:18]([N:15]2[CH2:16][CH2:17][N:12]([C:9]3[CH:8]=[N:7][C:6]([C:4](=[O:5])[CH3:35])=[CH:11][N:10]=3)[C@H:13]([CH3:33])[CH2:14]2)=[C:23]([CH3:24])[C:22]=1[CH3:25])[C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1

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 methoxy-methyl-amide (example 142, 450 mg, 0.975 mmol) is dissolved in THF (1 mL) and cooled to 0° C. A dropwise addition of methyl magnesium iodide (325 μL, 0.975 mmol) is added dropwise. Reaction is warmed to room temperature and continues to stir for 16 h. Add H2O (1 drop) and concentrate reaction mixture in vacuo. The residue is purified by flash chromatography on silica gel (60-100% EtOAc/Heptane and 0-8% MeOH/EtOAc) to afford the title compound (350 mg, 86%).

Workup

additionis added dropwise
customReaction
temperatureis warmed to room temperature
concentrationAdd H2O (1 drop) and concentrate
customreaction mixture in vacuo
customThe residue is purified by flash chromatography on silica gel (60-100% EtOAc/Heptane and 0-8% MeOH/EtOAc)

Sources & evidence

ORD record: ord-800833033cea45f293e8ccda7b888cf6
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09409871B2

Reaction notes

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