Methyl 6-aminonicotinate → 6-{3-cyclopentyl-2-[4-(2,6-difluoro-phenoxy)-6-oxo-6H-pyridazin-1-yl]-propionylamino}-nicotinic acid methyl ester

HRID 2381476Notes

Reaction equation

HRID 2381476 reaction equation
[CH:1]1([CH2:6][CH:7]([N:11]2[C:16](=[O:17])[CH:15]=[C:14]([O:18][C:19]3[C:24]([F:25])=[CH:23][CH:22]=[CH:21][C:20]=3[F:26])[CH:13]=[N:12]2)[C:8](O)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:27][O:28][C:29](=[O:37])[C:30]1[CH:35]=[CH:34][C:33]([NH2:36])=[N:32][CH:31]=1>>[CH3:27][O:28][C:29](=[O:37])[C:30]1[CH:35]=[CH:34][C:33]([NH:36][C:8](=[O:9])[CH:7]([N:11]2[C:16](=[O:17])[CH:15]=[C:14]([O:18][C:19]3[C:24]([F:25])=[CH:23][CH:22]=[CH:21][C:20]=3[F:26])[CH:13]=[N:12]2)[CH2:6][CH:1]2[CH2:5][CH2:4][CH2:3][CH2:2]2)=[N:32][CH:31]=1

Participants

3

Reactant 2

HCID 737487Methyl 6-aminonicotinateHCID 579193033-cyclopentyl-2-[4-(2,6-difluoro-phenoxy)-6-oxo-6H-pyridazin-1-yl]-propionic acid2×

Product 1

HCID 444658416-{3-cyclopentyl-2-[4-(2,6-difluoro-phenoxy)-6-oxo-6H-pyridazin-1-yl]-propionylamino}-nicotinic acid methyl ester

Procedure

Using the method described in Example 66, 3-cyclopentyl-2-[4-(2,6-difluoro-phenoxy)-6-oxo-6H-pyridazin-1-yl]-propionic acid (Intermediate 47) and 6-amino-nicotinic acid methyl ester afforded 6-{3-cyclopentyl-2-[4-(2,6-difluoro-phenoxy)-6-oxo-6H-pyridazin-1-yl]-propionylamino}-nicotinic acid methyl ester as a pale, yellow solid (720 mg, 66%); ES+-HRMS m/e calcd for C25H24N4O5F2 [M+H+] 499.1788 found 499.1784. 1H NMR (300 MHz, CDCl3) δ ppm 1.19 (br s, 2H) 1.41-1.91 (m, 7H) 2.13-2.44 (m, 2H) 3.93 (s, 3H) 5.65 (dd, J=8.6, 6.5 Hz, 1H) 6.04 (br s, 1H) 7.00-7.16 (m, 2H) 7.28-7.34 (m, 1H) 8.03 (d, J=2.4 Hz, 1H) 8.14-8.44 (m, 2H) 8.88 (s, 1H) 9.11 (br s, 1H).

Sources & evidence

ORD record
ord-2998a751352e4500952716ef8407ce9f
Source dataset
uspto-grants-2012_09
Patent number
US08258134B2

Reaction notes

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