Ethyl ((5-chlorothiophen-2-yl)sulfonyl)carbamate → 5-chloro-N-[({4-[6-(cyclopropylamino)-7-fluoro-1-oxoisoquinolin-2(1H)-yl]phenyl}amino)carbonyl]thiophene-2-sulfonamide

HRID 1593048Notes

Reaction equation

[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH:17]=[CH:16][C:15]3[C:10](=[CH:11][C:12]([F:22])=[C:13]([NH:18][CH:19]4[CH2:21][CH2:20]4)[CH:14]=3)[C:9]2=[O:23])=[CH:4][CH:3]=1.C([O:26][C:27](=O)[NH:28][S:29]([C:32]1[S:33][C:34]([Cl:37])=[CH:35][CH:36]=1)(=[O:31])=[O:30])C>C1(C)C=CC=CC=1>[Cl:37][C:34]1[S:33][C:32]([S:29]([NH:28][C:27]([NH:1][C:2]2[CH:7]=[CH:6][C:5]([N:8]3[CH:17]=[CH:16][C:15]4[C:10](=[CH:11][C:12]([F:22])=[C:13]([NH:18][CH:19]5[CH2:21][CH2:20]5)[CH:14]=4)[C:9]3=[O:23])=[CH:4][CH:3]=2)=[O:26])(=[O:31])=[O:30])=[CH:36][CH:35]=1

Participants

Conditions

Temperature: 110 °C

Procedure

A mixture of 2-(4-Amino-phenyl)-6-cyclopropylamino-7-fluoro-2H-isoquinolin-1-one (Example 11) (23 mg, 0.073 mmol) and (5-Chloro-thiophene-2-sulfonyl)-carbamic acid ethyl ester (Example 12) (28 mg, 0.10 mmol, 1.35 eq) in dry toluene (1.5 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 17 mg (46%) of pure 5-chloro-N-[({4-[6-(cyclopropylamino)-7-fluoro-1-oxoisoquinolin-2(1H)-yl]phenyl}amino)carbonyl]thiophene-2-sulfonamide. ES-MS (M+H)+=533, 535 (Cl).

Workup

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

Sources & evidence

ORD record: ord-36569bdfe69e4dea94f7b4a4cb6e2217
Source dataset: uspto-grants-2007_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07294635B2

Reaction notes

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