3-(4-Aminophenyl)-6-fluoro-7-(methylamino)-2,3-dihydrobenzo[e][1,3]oxazin-4-one → 1-(5-chlorothiophen-2-ylsulfonyl)-3-(4-(6-fluoro-7-(methylamino)-4-oxo-2H-benzo[e][1,3]oxazin-3(4H)-yl)phenyl)urea

HRID 1271049Notes

Reaction equation

[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:13](=[O:14])[C:12]3[CH:15]=[C:16]([F:21])[C:17]([NH:19][CH3:20])=[CH:18][C:11]=3[O:10][CH2:9]2)=[CH:4][CH:3]=1.C([O:24][C:25](=O)[NH:26][S:27]([C:30]1[S:31][C:32]([Cl:35])=[CH:33][CH:34]=1)(=[O:29])=[O:28])C>O1CCOCC1>[Cl:35][C:32]1[S:31][C:30]([S:27]([NH:26][C:25]([NH:1][C:2]2[CH:3]=[CH:4][C:5]([N:8]3[C:13](=[O:14])[C:12]4[CH:15]=[C:16]([F:21])[C:17]([NH:19][CH3:20])=[CH:18][C:11]=4[O:10][CH2:9]3)=[CH:6][CH:7]=2)=[O:24])(=[O:29])=[O:28])=[CH:34][CH:33]=1

Participants

Conditions

Temperature: 110 °C

Procedure

A mixture of 3-(4-aminophenyl)-6-fluoro-7-(methylamino)-2,3-dihydrobenzo[e][1,3]oxazin-4-one (Ex. 4) (130 mg, 0.45 mmol) and (5-Chloro-thiophene-2-sulfonyl)-carbamic acid ethyl ester (150 mg, 0.53 mmol, 1.2 eq) in dry 1,4-dioxan (3 mL) was heated at 110° C. for 2 hr. Upon cooling, the reaction was concentrated in vacuo and the crude residue was purified by HPLC (C-18) to give 86 mg (37%) of pure 1-(5-chlorothiophen-2-ylsulfonyl)-3-(4-(6-fluoro-7-(methylamino)-4-oxo-2H-benzo[e][1,3]oxazin-3(4H)-yl)phenyl)urea. RP-HPLC: 2.49 min; ES-MS (M+H)+=511.0; 1H-NMR (MeOH-d4) δ (ppm): 2.8 (s, 3 H), 5.4 (s, 2 H), 6.2 (d, 1 H), 6.9 (d, 2 H), 7.1 (d, 2 H), 7.3 (d, 1 H), 7.4 (d, 1 H), 7.5 (d, 2 H).

Workup

temperatureUpon cooling
concentrationthe reaction was concentrated in vacuo
customthe crude residue was purified by HPLC (C-18)

Sources & evidence

ORD record: ord-879e8416889040fb8f8d2a113141ba6f
Source dataset: uspto-grants-2007_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07205296B2

Reaction notes

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