2-chloro-N-[(3-fluorophenyl)-methyl]-4-methyl-6-morpholin-4-yl-pyridine-3-carboxylic acid amide → Ethyl-N-[(3-fluorophenyl)-methyl]-4-methyl-6-morpholin-4-yl-pyridine-3-carboxylic acid amide

HRID 1753874Notes

Reaction equation

Cl[C:2]1[C:7]([C:8]([NH:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=2)=[O:9])=[C:6]([CH3:19])[CH:5]=[C:4]([N:20]2[CH2:25][CH2:24][O:23][CH2:22][CH2:21]2)[N:3]=1.[CH2:26]([Mg]Br)[CH3:27]>C1COCC1.Cl[Ni]1(Cl)[P](C2C=CC=CC=2)(C2C=CC=CC=2)CCC[P]1(C1C=CC=CC=1)C1C=CC=CC=1>[CH2:26]([C:2]1[C:7]([C:8]([NH:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=2)=[O:9])=[C:6]([CH3:19])[CH:5]=[C:4]([N:20]2[CH2:25][CH2:24][O:23][CH2:22][CH2:21]2)[N:3]=1)[CH3:27]

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of 200 mg (0.55 mmol) 2-chloro-N-[(3-fluorophenyl)-methyl]-4-methyl-6-morpholin-4-yl-pyridine-3-carboxylic acid amide (synthesis is described in section a) of example 9) in THF (5 ml) were added 30 mg (0.055 mmol) Ni(dppp)Cl2 and 330 μl (0.66 mmol, 2M in THF) ethylmagnesiumbromide. The RM was heated to 80° C. for 8 h, followed by quenching with a sat. aq. NH4Cl sol. and extraction with EtOAc (3×20 ml). The combined organic layers were washed with water and brine, dried over Na2SO4 and concentrated in vacuo. Purification of the residue by CC (hexane/EtOAc 7:3) provided 50 mg (0.14 mmol, 25%) Ethyl-N-[(3-fluorophenyl)-methyl]-4-methyl-6-morpholin-4-yl-pyridine-3-carboxylic acid amide (example 22). [M+H]+358.2.

Workup

customby quenching with a sat. aq. NH4Cl sol. and extraction with EtOAc (3×20 ml)
washThe combined organic layers were washed with water and brine
dry with materialdried over Na2SO4
concentrationconcentrated in vacuo
customPurification of the residue by CC (hexane/EtOAc 7:3)

Sources & evidence

ORD record: ord-7f7e7777a65543eca527a60892333ff6
Source dataset: uspto-grants-2015_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09168259B2

Reaction notes

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