Lithium Hydroxide → 3-(3-(4-Fluoro-2-methoxyphenoxy)quinoxaline-2-carboxamido)benzoic acid

HRID 2280579Notes

Reaction equation

[NH2:1][C:2]1[CH:3]=[C:4]([CH:10]=[CH:11][CH:12]=1)[C:5]([O:7]CC)=[O:6].[F:13][C:14]1[CH:33]=[CH:32][C:17]([O:18][C:19]2[C:20]([C:29](O)=[O:30])=[N:21][C:22]3[C:27]([N:28]=2)=[CH:26][CH:25]=[CH:24][CH:23]=3)=[C:16]([O:34][CH3:35])[CH:15]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(CC)CC.[OH-].[Li+]>CN(C=O)C>[F:13][C:14]1[CH:33]=[CH:32][C:17]([O:18][C:19]2[C:20]([C:29]([NH:1][C:2]3[CH:3]=[C:4]([CH:10]=[CH:11][CH:12]=3)[C:5]([OH:7])=[O:6])=[O:30])=[N:21][C:22]3[C:27]([N:28]=2)=[CH:26][CH:25]=[CH:24][CH:23]=3)=[C:16]([O:34][CH3:35])[CH:15]=1

Participants

Conditions

Temperature: 50 °C

Procedure

To ethyl 3-aminobenzoate (18.9 mg, 0.11 mmol) in DMF (0.3 mL) was added 3-(4-fluoro-2-methoxy-phenoxy)quinoxaline-2-carboxylic acid (30 mg, 0.09 mmol), HATU (54.4 mg, 0.14 mmol) and Et3N (39.9 μL, 0.29 mmol). The reaction is stirred at 50° C. for 2 hours. Lithium hydroxide (45 μL of 4M, 0.18 mmol) was added and the reaction was stirred at 25° C. overnight. The reaction was filtered and purified by reverse phase HPLC using a gradient of methanol in water (1-99%) and ammonium formate as a modifier to yield 3-(3-(4-fluoro-2-methoxyphenoxy)quinoxaline-2-carboxamido)benzoic acid (36) (16.4 mg, 42%). ESI-MS m/z calc. 433.11, found 434.0 (M+1)+; Retention time: 1.56 minutes (2.5 minutes run). 1H NMR (400 MHz, DMSO-d6) δ 11.10 (s, 1H), 8.39 (t, J=1.9 Hz, 1H), 8.18 (dd, J=8.0, 1.6 Hz, 1H), 7.99-7.92 (m, 1H), 7.87-7.68 (m, 4H), 7.48 (t, J=7.9 Hz, 1H), 7.35 (dd, J=8.8, 5.9 Hz, 1H), 7.16 (dd, J=10.7, 2.9 Hz, 1H), 6.88 (td, J=8.5, 2.9 Hz, 1H), 3.71 (s, 3H) ppm.

Workup

stirringthe reaction was stirred at 25° C. overnight
filtrationThe reaction was filtered
custompurified by reverse phase HPLC

Sources & evidence

ORD record: ord-7608b9a61d4f4f0989d59078e1d435f2
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09139529B2

Reaction notes

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