Triethylamine → 6-Chloro-4-[(2-ethoxycarbonyl-ethyl)-indan-5-yl-amino]-nicotinic acid ethyl ester

HRID 1989031Notes

Reaction equation

[CH2:1]([O:3][C:4](=[O:13])[C:5]1[C:10](Cl)=[CH:9][C:8]([Cl:12])=[N:7][CH:6]=1)[CH3:2].[CH2:14]([O:16][C:17](=[O:30])[CH2:18][CH2:19][NH:20][C:21]1[CH:22]=[C:23]2[C:27](=[CH:28][CH:29]=1)[CH2:26][CH2:25][CH2:24]2)[CH3:15].C(N(CC)CC)C>CN(C=O)C>[CH2:1]([O:3][C:4](=[O:13])[C:5]1[C:10]([N:20]([CH2:19][CH2:18][C:17]([O:16][CH2:14][CH3:15])=[O:30])[C:21]2[CH:22]=[C:23]3[C:27](=[CH:28][CH:29]=2)[CH2:26][CH2:25][CH2:24]3)=[CH:9][C:8]([Cl:12])=[N:7][CH:6]=1)[CH3:2]

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of 4,6-dichloro-nicotinic acid ethyl ester (2 g, 9 mmol) and 3-(indan-5-ylamino)-propionic acid ethyl ester (from Example 1 (A), 2.3 g, 10 mmol) in 5 mL of DMF was added triethylamine (2 g, 20 mmol). The mixture was stirred at 100° C. for 48 hours. The reaction was cooled, quenched with water, and extracted 3 times with EtOAc. The organic layer was dried over Na2SO4 and concentrated in vacuo. Flash chromatography (EtOAc/Hexanes, 2:10 v/v) afforded the title compound as a white solid (1.6 g, 44%). 1H NMR (400 MHz, CDCl3) δ (ppm): 8.22 (s, 1H), 7.15 (d, J=8.0 Hz, 1H), 6.92 (s, 1H), 6.85 (m, 2H), 4.03-4.15 (m, 4H), 3.74 (q, J=7.1 Hz, 2H), 2.85 (t, J=7.4 Hz, 4H), 2.64 (m, 2H), 2.07 (m, 2H), 1.23 (t, J=7.1 Hz, 3H), 1.08 (t, J=7.1 Hz, 3H).

Workup

temperatureThe reaction was cooled
customquenched with water
extractionextracted 3 times with EtOAc
dry with materialThe organic layer was dried over Na2SO4
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-ea1c10b3bf054673a2a0d5fb63de055e
Source dataset: uspto-grants-2010_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07642270B2

Reaction notes

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