3-{Ethyl[1-(propan-2-yl)piperidin-4-yl]amino}-2-methyl-5-(trifluoromethyl)benzoic acid → 5-chloro-3-(ethyl(1-methylazetidin-3-yl)amino)-2-methyl-N-((6-methyl-2-oxo-4-propyl-1,2-dihydropyridin-3-yl)methyl)benzamide formate

HRID 2208964Notes

Reaction equation

HRID 2208964 reaction equation
ClC1C=C(N(CC)C2CN(C)C2)C(C)=C(C=1)[C:7]([O:9]C)=[O:8].[Cl:21][C:22]1[CH:23]=[C:24]([N:32]([CH2:38][CH3:39])[CH:33]2[CH2:36][N:35]([CH3:37])[CH2:34]2)[C:25]([CH3:31])=[C:26]([CH:30]=1)[C:27]([OH:29])=O.C(N(C1CCN(C(C)C)CC1)C1C(C)=C(C=C(C(F)(F)F)C=1)C(O)=O)C.Cl.[NH2:67][CH2:68][C:69]1[C:70](=[O:79])[NH:71][C:72]([CH3:78])=[CH:73][C:74]=1[CH2:75][CH2:76][CH3:77].CC1C=C(C)NC(=O)C=1CNC(=O)C1C=C(C(F)(F)F)C=C(N(CC)C2CCN(C)CC2)C=1C>>[CH:7]([OH:9])=[O:8].[Cl:21][C:22]1[CH:23]=[C:24]([N:32]([CH2:38][CH3:39])[CH:33]2[CH2:36][N:35]([CH3:37])[CH2:34]2)[C:25]([CH3:31])=[C:26]([CH:30]=1)[C:27]([NH:67][CH2:68][C:69]1[C:70](=[O:79])[NH:71][C:72]([CH3:78])=[CH:73][C:74]=1[CH2:75][CH2:76][CH3:77])=[O:29]

Participants

6

Reactant 5

HCID 708738793-{Ethyl[1-(propan-2-yl)piperidin-4-yl]amino}-2-methyl-5-(trifluoromethyl)benzoic acidHCID 708739305-Chloro-3-(ethyl(1-methylazetidin-3-yl)amino)-2-methylbenzoic acid2×HCID 708741233-AMinoMethyl-6-Methyl-4-propyl-1H-pyridin-2-one hydrochlorideHCID 70913333N-[(4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-3-[ethyl(1-methylpiperidin-4-yl)amino]-2-methyl-5-(trifluoromethyl)benzamideHCID 86719581Methyl 5-chloro-3-(ethyl(1-methylazetidin-3-yl)amino)-2-methylbenzoate

Product 1

HCID 708741255-chloro-3-(ethyl(1-methylazetidin-3-yl)amino)-2-methyl-N-((6-methyl-2-oxo-4-propyl-1,2-dihydropyridin-3-yl)methyl)benzamide formate

Procedure

Methyl 5-chloro-3-(ethyl(1-methylazetidin-3-yl)amino)-2-methylbenzoate was hydrolyzed to 5-chloro-3-(ethyl(1-methylazetidin-3-yl)amino)-2-methylbenzoic acid following the same preparation method for 3-{Ethyl[1-(propan-2-yl)piperidin-4-yl]amino}-2-methyl-5-(trifluoromethyl)benzoic acid from its corresponding carboxylate. The crude 5-chloro-3-(ethyl(1-methylazetidin-3-yl)amino)-2-methylbenzoic acid was then coupled with 3-(Aminomethyl)-6-methyl-4-propyl-1,2-dihydropyridin-2-one HCl salt prepared earlier following the preparation method described for N-[(4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-3-[ethyl(1-methylpiperidin-4-yl)amino]-2-methyl-5-(trifluoromethyl)benzamide. After purification by reverse phase HPLC/MS (CAN-H2O containing 0.1% formic acid), the titled compound was obtained. 1H-NMR (500 MHz, CD3OD) δ ppm 8.58-8.24 (br, 1H), 7.15 (d, J=2.0 Hz, 1H), 7.08 (d, J=2.0 Hz, 1H), 6.14 (s, 1H), 4.48 (s, 2H), 4.41-4.34 (m, 1H), 4.25 (br, 2H), 3.85 (br, 2H), 3.00 (q, J=7.0 Hz, 2H), 2.92 (s, 3H), 2.72-2.66 (m, 2H), 2.34 (s, 3H), 2.26 (s, 3H), 1.70-1.61 (m, 2H), 1.04 (t, J=7.2 Hz, 3H), 0.91 (t, J=7.0 Hz, 3H); MS (ES) (M+H) 445.48.

Workup

  1. customprepared earlier
  2. customthe preparation method
  3. customAfter purification by reverse phase HPLC/MS (CAN-H2O containing 0.1% formic acid)

Sources & evidence

ORD record
ord-11e27ed6c0554c62a805265b0f4bc187
Source dataset
uspto-grants-2016_06
Patent number
US09376422B2

Reaction notes

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