Potassium Carbonate → 4-Amino-2-(2,2-dioxo-2,3,3a,7a-tetrahydro-1H-2lambda6-benzo[c]thiophen-5-yl)-thieno[3,2-c]pyridine-7-carboxylic acid amide

HRID 1868308

Reaction equation

Br[C:2]1[CH:12]=[CH:11][C:5]2[CH2:6][S:7](=[O:10])(=[O:9])[CH2:8][C:4]=2[CH:3]=1.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.CC([O-])=O.[K+].C([O-])([O-])=O.[K+].[K+].[NH2:42][C:43]1[C:48]2[CH:49]=[C:50](Br)[S:51][C:47]=2[C:46]([C:53]([NH2:55])=[O:54])=[CH:45][N:44]=1>CS(C)=O.O>[NH2:42][C:43]1[C:48]2[CH:49]=[C:50]([C:2]3[CH:12]=[CH:11][CH:5]4[CH2:6][S:7](=[O:10])(=[O:9])[CH2:8][CH:4]4[CH:3]=3)[S:51][C:47]=2[C:46]([C:53]([NH2:55])=[O:54])=[CH:45][N:44]=1

Participants

Conditions

Temperature: 85 °C

Procedure

To a stirred solution 5-bromo-1,3-dihydro-benzo[c]thiophene 2,2-dioxide (160 mg, 0.65 mmol) 67 (Salor, Milwaukee, Wis.) in DMSO (1 mL) was added bis(pinacolato)diboron (178 mg, 0.70 mmol), KOAc (159 mg, 1.6 mmol) and Pd(dppf)Cl2 DCM complex (22 mg, 0.027 mmol). The mixture was degassed with N2 and heated at 85° C. for 2 h then DMSO (2 mL), H2O (0.5 mL), K2CO3 (223 mg, 1.6 mmol) and 4-amino-2-bromo-thieno[3,2-c]pyridine-7-carboxylic acid amide H2SO4 salt 17 (200 mg, 0.54 mmol) were added. The mixture was stirred at 85° C. for a further 12 h then filtered. The residue was washed with DMSO (2 mL) and the filtrate purified by reverse phase preparative HPLC to yield 68 as a white solid. 1H-NMR (400 MHz, d6-DMSO) δ 8.31 (s, 1H), 8.24 (s, 1H), 8,19 (bs, 1H), 7.97-7.92 (m, 3H), 7.85 (d, 1H), 4.78 (s, 2H), 4.71 (s, 2H).

Workup

customThe mixture was degassed with N2
filtrationthen filtered
washThe residue was washed with DMSO (2 mL)
customthe filtrate purified by reverse phase preparative HPLC

Sources & evidence

ORD record: ord-bbc7da129029491fa8c2b79debaa811c
Source dataset: uspto-grants-2009_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07635695B2

Linked notes

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