Aniline → (R)-4-(4,5-Dimethyl-6-phenylamino-pyridazin-3-yl)-2-methyl-3,4,5,6-tetra-hydro-2H-[1,2']bipyrazinyl-5'-carboxylic acid penylamide

HRID 1479944Notes

Reaction equation

HRID 1479944 reaction equation
CO[C:3]([C:5]1[N:6]=[CH:7][C:8]([N:11]2[CH2:16][CH2:15][N:14]([C:17]3[N:18]=[N:19][C:20](Cl)=[C:21]([CH3:24])[C:22]=3[CH3:23])[CH2:13][C@H:12]2[CH3:26])=[N:9][CH:10]=1)=[O:4].[NH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>>[C:28]1([NH:27][C:3]([C:5]2[N:6]=[CH:7][C:8]([N:11]3[CH2:16][CH2:15][N:14]([C:17]4[N:18]=[N:19][C:20]([NH:27][C:28]5[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=5)=[C:21]([CH3:24])[C:22]=4[CH3:23])[CH2:13][C@H:12]3[CH3:26])=[N:9][CH:10]=2)=[O:4])[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1

Participants

3

Reactant 2

HCID 6115AnilineHCID 59191626(R)-4-(6-Chloro-4,5-dimethyl-pyridazin-3-yl)-2-methyl-3,4,5,6-tetrahydro-2H [1,2']bipyrazinyl-5'-carboxylic acid methyl ester2×

Product 1

HCID 59191632(R)-4-(4,5-Dimethyl-6-phenylamino-pyridazin-3-yl)-2-methyl-3,4,5,6-tetra-hydro-2H-[1,2']bipyrazinyl-5'-carboxylic acid penylamide

Conditions

Temperature
190 °C

Procedure

To (R)-4-(6-chloro-4,5-dimethyl-pyridazin-3-yl)-2-methyl-3,4,5,6-tetrahydro-2H-[1,2]bipyrazinyl-5′-carboxylic acid methyl ester (compound 54, 250 mg, 0.663 mmol) is added aniline (2.4 mL, 26.5 mmol) in a microwave tube. The reaction mixture is heated at 190° C. for 30 min in a microwave reactor. The reaction mixture is loaded on silica gel and purified by flash chromatography, eluting with 50%-100% EtOAc: heptane for six column volumes, followed with 3%-10% MeOH in DCM. Both example 3 and 4 are collected and concentrated to afford white solids.

Workup

  1. custompurified by flash chromatography
  2. washeluting with 50%-100% EtOAc
  3. customBoth example 3 and 4 are collected
  4. concentrationconcentrated
  5. customto afford white solids

Sources & evidence

ORD record
ord-b819828d5d3843c5a58aa1c5dbd7ee73
Source dataset
uspto-grants-2016_08
Patent number
US09409871B2

Reaction notes

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