Methyl 2-aminopyridine-3-carboxylate → 6-{3-[7-Fluoro-2-(4-fluoro-benzyl)-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-propionylamino}-nicotinic acid methyl ester

HRID 2402296Notes

Reaction equation

HRID 2402296 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[CH:9]([CH2:11][CH2:12][C:13]([NH:15][C:16]1[CH:24]=[CH:23][C:19]([C:20]([OH:22])=[O:21])=[CH:18][N:17]=1)=[O:14])[N:8]([CH2:25][C:26]1[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=1)[C:7]2=[O:33].[CH3:34]OC(=O)C1C=CC=NC=1N>>[CH3:34][O:21][C:20](=[O:22])[C:19]1[CH:23]=[CH:24][C:16]([NH:15][C:13](=[O:14])[CH2:12][CH2:11][CH:9]2[C:10]3[C:6](=[CH:5][CH:4]=[CH:3][C:2]=3[F:1])[C:7](=[O:33])[N:8]2[CH2:25][C:26]2[CH:27]=[CH:28][C:29]([F:32])=[CH:30][CH:31]=2)=[N:17][CH:18]=1

Participants

3

Reactant 2

HCID 351633Methyl 2-aminopyridine-3-carboxylateHCID 160587176-{3-[7-Fluoro-2-(4-fluorobenzyl)-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-propionylamino}-nicotinic acid

Product 1

HCID 588698136-{3-[7-Fluoro-2-(4-fluoro-benzyl)-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-propionylamino}-nicotinic acid methyl ester

Procedure

The product from Example 11, Part D (331 mg, 1 mmol) and 2-aminonicotinic acid methyl ester (316 mg, 2.1 mmol) were converted to the title compound in a manner analogous to the method described in Example 7, Part E without crystallization (269 mg, 58%). 1H NMR (300 MHz, CDCl3) δ 8.83 (d, J=2 Hz, 1H), 8.27 (dd, J=8 Hz, 2 Hz, 1H), 8.16 (d, J=9 Hz, 1H), 7.87 (br s, 1H), 7.69 (d, J=7 Hz, 1H), 7.46 (m, 1H), 7.31 (m, 2H), 7.20 (t, J=9 Hz, 1H), 7.02 (t, J=9 Hz, 2H), 5.25 (d, J=15 Hz, 1H), 4.70 (m, 1H), 4.25 (d, J=15 Hz, 1H), 3.92 (s, 3H), 2.52 (m, 2H), 1.98 (m, 2H). MS: m/z (MH+) 466.

Sources & evidence

ORD record
ord-944e59a0bb2345839467d067d54356ab
Source dataset
uspto-grants-2014_08
Patent number
US08796313B2

Reaction notes

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