Ethyl bromoacetate → ethyl 2-(5-fluoro-2-(6-(N-(4-methoxybenzyl)-N-(thiazol-2-yl)sulfamoyl)isoquinolin-1-yl)phenoxy)acetate

HRID 1473615Notes

Reaction equation

C([O-])([O-])=O.[Cs+].[Cs+].Br[CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10].[F:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]2[C:30]3[C:25](=[CH:26][C:27]([S:31]([N:34]([CH2:40][C:41]4[CH:46]=[CH:45][C:44]([O:47][CH3:48])=[CH:43][CH:42]=4)[C:35]4[S:36][CH:37]=[CH:38][N:39]=4)(=[O:33])=[O:32])=[CH:28][CH:29]=3)[CH:24]=[CH:23][N:22]=2)=[C:17]([OH:49])[CH:16]=1>CN(C=O)C.CCOC(C)=O>[F:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]2[C:30]3[C:25](=[CH:26][C:27]([S:31](=[O:32])(=[O:33])[N:34]([CH2:40][C:41]4[CH:46]=[CH:45][C:44]([O:47][CH3:48])=[CH:43][CH:42]=4)[C:35]4[S:36][CH:37]=[CH:38][N:39]=4)=[CH:28][CH:29]=3)[CH:24]=[CH:23][N:22]=2)=[C:17]([CH:16]=1)[O:49][CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10]

Participants

Conditions

Temperature: 60 °C

Procedure

A mixture of Cs2CO3 (0.281 g, 0.863 mmol), ethyl bromoacetate (0.048 ml, 0.431 mmol) and 1-(4-fluoro-2-hydroxyphenyl)-N-(4-methoxybenzyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide (From Step 1 in Example 189; 0.15 g, 0.288 mmol) in DMF (2.88 ml) was stirred at 60° C. for 16 h. The reaction mixture was diluted with EtOAc (75 mL) and washed with water (2×50 mL). The organic layer was dried over anhydrous sodium sulfate, concentrated and purified by silica gel chromatography (25 g column), eluting with EtOAc:Hex: 0-50% to obtain ethyl 2-(5-fluoro-2-(6-(N-(4-methoxybenzyl)-N-(thiazol-2-yl)sulfamoyl)isoquinolin-1-yl)phenoxy)acetate as light yellow solid. m/z (ESI) 608.3 (M+H)+.

Workup

washwashed with water (2×50 mL)
dry with materialThe organic layer was dried over anhydrous sodium sulfate
concentrationconcentrated
custompurified by silica gel chromatography (25 g column)
washeluting with EtOAc

Sources & evidence

ORD record: ord-e52792ab94794a89865957a2e5992455
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09012443B2

Reaction notes

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