3-(Aminomethyl)-5-fluoro-4-isopropyl-6-methylpyridin-2(1H)-one → tert-Butyl 4-(5-(3-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-5-(((5-fluoro-4-isopropyl-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)carbamoyl)-4-methylphenyl)pyridin-2-yl)piperazine-1-carboxylate

HRID 1959328Notes

Reaction equation

HRID 1959328 reaction equation
[CH2:1]([N:3]([CH:34]1[CH2:39][CH2:38][O:37][CH2:36][CH2:35]1)[C:4]1[CH:5]=[C:6]([C:15]2[CH:16]=[CH:17][C:18]([N:21]3[CH2:26][CH2:25][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:23][CH2:22]3)=[N:19][CH:20]=2)[CH:7]=[C:8]([C:11](OC)=[O:12])[C:9]=1[CH3:10])[CH3:2].[NH2:40][CH2:41][C:42]1[C:43](=[O:53])[NH:44][C:45]([CH3:52])=[C:46]([F:51])[C:47]=1[CH:48]([CH3:50])[CH3:49]>>[CH2:1]([N:3]([CH:34]1[CH2:39][CH2:38][O:37][CH2:36][CH2:35]1)[C:4]1[CH:5]=[C:6]([C:15]2[CH:16]=[CH:17][C:18]([N:21]3[CH2:22][CH2:23][N:24]([C:27]([O:29][C:30]([CH3:31])([CH3:33])[CH3:32])=[O:28])[CH2:25][CH2:26]3)=[N:19][CH:20]=2)[CH:7]=[C:8]([C:11](=[O:12])[NH:40][CH2:41][C:42]2[C:43](=[O:53])[NH:44][C:45]([CH3:52])=[C:46]([F:51])[C:47]=2[CH:48]([CH3:50])[CH3:49])[C:9]=1[CH3:10])[CH3:2]

Participants

3

Reactant 2

HCID 866848973-(Aminomethyl)-5-fluoro-4-isopropyl-6-methylpyridin-2(1H)-oneHCID 123822786tert-Butyl 4-(5-(3-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-5-(methoxycarbonyl)-4-methylphenyl)pyridin-2-yl)piperazine-1-carboxylate

Product 1

HCID 70872613tert-Butyl 4-(5-(3-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-5-(((5-fluoro-4-isopropyl-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)carbamoyl)-4-methylphenyl)pyridin-2-yl)piperazine-1-carboxylate

Procedure

Hydrolysis of tert-Butyl 4-(5-(3-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-5-(methoxycarbonyl)-4-methylphenyl)pyridin-2-yl)piperazine-1-carboxylate following the similar methods for examples described earlier resulted in a crude corresponding carboxylic acid 5-(6-(4-(tert-butoxycarbonyl)piperazin-1-yl)pyridin-3-yl)-3-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-2-methylbenzoic acid. This acid was then coupled with 3-(aminomethyl)-5-fluoro-4-isopropyl-6-methylpyridin-2(1H)-one following similar methods described earlier. After purification by reverse phase HPLC (ACN-H2O containing 0.1% formic acid), the titled compound was obtained. 1H-NMR (400 MHz, CD3OD) δ ppm 8.33 (d, J=2.6 Hz, 1H), 7.81 (dd, J=2.6, 8.8 Hz, 1H), 7.41 (d, J=2.0 Hz, 1H), 7.26 (d, J=2.0 Hz, 1H), 6.91 (d, J=8.8 Hz, 1H), 4.54 (s, 2H), 3.92 (m, 2H), 3.46-3.56 (m, 9H), 3.34 (m, 2H), 3.07-3.18 (m, 3H), 2.33 (s, 3H), 2.24 (d, J=3.2 Hz, 3H), 1.74-1.77 (m, 2H), 1.62-1.69 (m, 2H), 1.49 (s, 9H), 1.37 (dd, J=1.6, 6.8 Hz, 6H), 0.90 (t, J=6.8 Hz, 3H); MS (ES) (M+H) 705.7.

Workup

  1. customdescribed earlier resulted in a crude corresponding carboxylic acid 5-(6-(4-(tert-butoxycarbonyl)piperazin-1-yl)pyridin-3-yl)-3-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-2-methylbenzoic acid
  2. customAfter purification by reverse phase HPLC (ACN-H2O containing 0.1% formic acid)

Sources & evidence

ORD record
ord-d3fa6761a66b41c4892e8c08ffa1ba7c
Source dataset
uspto-grants-2013_04
Patent number
US08410088B2

Reaction notes

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