2,6-Lutidine → 1-[5-(6-Chloro-2-oxo-4-phenyl-1,2-dihydro-quinolin-3-yl)-isoxazol-3-yl]-3-(2-morpholin-4-yl-ethyl)-urea

HRID 2053443Notes

Reaction equation

[NH2:1][C:2]1[CH:6]=[C:5]([C:7]2[C:8](=[O:24])[NH:9][C:10]3[C:15]([C:16]=2[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[CH:14][C:13]([Cl:23])=[CH:12][CH:11]=3)[O:4][N:3]=1.N1C(C)=CC=CC=1C.Cl[C:34](OC1C=CC([N+]([O-])=O)=CC=1)=[O:35].[N:46]1([CH2:52][CH2:53][NH2:54])[CH2:51][CH2:50][O:49][CH2:48][CH2:47]1>CC(N(C)C)=O>[Cl:23][C:13]1[CH:14]=[C:15]2[C:10](=[CH:11][CH:12]=1)[NH:9][C:8](=[O:24])[C:7]([C:5]1[O:4][N:3]=[C:2]([NH:1][C:34]([NH:54][CH2:53][CH2:52][N:46]3[CH2:51][CH2:50][O:49][CH2:48][CH2:47]3)=[O:35])[CH:6]=1)=[C:16]2[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

Conditions

Temperature: 25 °C

Procedure

A flask charged with 3-(3-amino-isoxazol-5-yl)-6-chloro-4-phenyl-1H-quinolin-2-one (example 59)(15 mg, 0.045 mmol), 2,6-lutidine (5.5 mg, 0.052 mmol), 4-nitrophenyl chloroformate (10 mg, 0.05 mmol), and DMA (0.3 mL) was stirred at 25° C. for 10 mins and then 2-morpholin-4-yl-ethylamine (12 mg, 0.092 mmol) was added and stirring continued for 30 mins. The reaction was concentrated and the title compound was purified by RP-HPLC, eluting with 20-50% CH3CN in 0.1% TFA/H2O over 10 mins to give 6 mg (22%) the title cpd as a TFA salt. 1H NMR (400 MHz, CD3OD) δ 7.62 (dd, 1H), 7.52 (m, 3H), 7.44 (m, 2H), 7.30 (m, 2H), 7.12 (d, 1H), 6.60 (s, 1H), 3.72 (m, 4H), 3.40 (m, 2H), 2.52 (m, 6H). Mass spectrum (ESI, m/z) calcd. for C25H24ClN5O4 493.1, found 494.0 (M+H).

Workup

stirringstirring
waitcontinued for 30 mins
concentrationThe reaction was concentrated
customthe title compound was purified by RP-HPLC
washeluting with 20-50% CH3CN in 0.1% TFA/H2O over 10 mins

Sources & evidence

ORD record: ord-7b4ccb5598a3441bab5761e80787847d
Source dataset: uspto-grants-2008_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07326788B2

Reaction notes

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