Potassium Carbonate → N-(2-chloro-4-(methylcarbamoyl)phenyl)-9-cyano-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide

HRID 1949842Notes

Reaction equation

[C:1]([C:3]1[CH:4]=[CH:5][C:6]2[O:15][CH2:14][CH2:13][C:12]3[CH:11]=[C:10]([C:16]([OH:18])=O)[S:9][C:8]=3[C:7]=2[CH:19]=1)#[N:2].S(Cl)(Cl)=O.C(=O)([O-])[O-].[K+].[K+].[Cl:30][C:31]1[CH:32]=[C:33]([CH:38]=[CH:39][C:40]=1[NH:41][CH3:42])[C:34]([NH:36][CH3:37])=[O:35]>C1(C)C=CC=CC=1.C(#N)C.O>[Cl:30][C:31]1[CH:32]=[C:33]([C:34](=[O:35])[NH:36][CH3:37])[CH:38]=[CH:39][C:40]=1[N:41]([CH3:42])[C:16]([C:10]1[S:9][C:8]2[C:7]3[CH:19]=[C:3]([C:1]#[N:2])[CH:4]=[CH:5][C:6]=3[O:15][CH2:14][CH2:13][C:12]=2[CH:11]=1)=[O:18]

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of 9-cyano-4,5-dihydro-6-oxa-1-thia-benzo[e]azulene-2-carboxylic acid (300 mg) in toluene (10 mL) was added thionyl chloride (2 mL) and the reaction heated at 80° C. for 2 h. After cooling to room temperature, the solvent was reduced in vacuo and the residue redissolved in acetonitrile (10 mL). Potassium carbonate (306 mg) and 3-chloro-N-methyl-4-methylamino-benzamide from Example 21 (263 mg) were added and the reaction stirred at room temperature for 16 h. Water (20 mL) was added and the product extracted into ethyl acetate (2×20 mL). The organics were dried (MgSO4), reduced in vacuo and purified on silica to give 298. NMR: (CDCl3): 2.95-2.98 (5 H, m), 3.31 (3 H, s, Me), 4.19-4.21 (2 H, m), 6.10 (1 H, s, NH), 0.76 (1 H, s, Ar), 6.96 (1 H, d, J 8.4, Ar), 7.31-7.36 (2 H, m, Ar), 7.64-7.67 (2 H, m, Ar) and 7.87 (1 H, d, J 1.8, Ar). MS: (ESI+) MH+ 451.25

Workup

temperatureAfter cooling to room temperature
extractionthe product extracted into ethyl acetate (2×20 mL)
dry with materialThe organics were dried (MgSO4)
custompurified on silica

Sources & evidence

ORD record: ord-b9b4cfd8a3a541a8869b68d84874e4a1
Source dataset: uspto-grants-2013_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08399690B2

Reaction notes

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