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

HRID 1753883Notes

Reaction equation

C(O[C:4]([C:6]1[C:7]([N:19]([CH2:21][CH3:22])[CH3:20])=[N:8][C:9]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)=[CH:10][C:11]=1[CH3:12])=[O:5])C.[F:23][C:24]1[CH:31]=[CH:30][C:27]([CH2:28][NH2:29])=[CH:26][CH:25]=1.C[Al](C)C.[OH-].[Na+]>C1(C)C=CC=CC=1.O.CCOC(C)=O>[CH2:21]([N:19]([CH3:20])[C:7]1[C:6]([C:4]([NH:29][CH2:28][C:27]2[CH:30]=[CH:31][C:24]([F:23])=[CH:25][CH:26]=2)=[O:5])=[C:11]([CH3:12])[CH:10]=[C:9]([N:13]2[CH2:14][CH2:15][O:16][CH2:17][CH2:18]2)[N:8]=1)[CH3:22]

Participants

Conditions

Temperature: 120 °C

Procedure

A solution of 249 mg (0.81 mmol) 2-(ethyl(methyl)amino)-4-methyl-6-morpholino-pyridine-3-carboxylic acid ethylester and 924 μl (8.1 mmol) 4-fluoro-benzylamine in toluene (17 ml) was treated with 2.85 ml (2M in toluene, 5.7 mmol) AlMe3 and was subsequently heated to 120° C. for 4 d. Then the solution was diluted with water, a 1M aq. NaOH sol. and EtOAc. The organic layer was separated, washed with a 2M aq. NaOH sol. and brine, dried over MgSO4 and concentrated in vacuo. Purification of the residue by CC (hexane/EtOAc 3:1) provided 127 mg (0.33 mmol, 40%) 2-(Ethyl-methyl-amino)-N-[(4-fluorophenyl)-methyl]-4-methyl-6-morpholin-4-yl-pyridine-3-carboxylic acid amide (example 174). [M+H]+387.2

Workup

customThe organic layer was separated
washwashed with a 2M aq. NaOH sol. and brine
dry with materialdried over MgSO4
concentrationconcentrated in vacuo
customPurification of the residue by CC (hexane/EtOAc 3:1)

Sources & evidence

ORD record: ord-4b46590adde344d1986f9b553c464b6d
Source dataset: uspto-grants-2015_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09168259B2

Reaction notes

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