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

HRID 1949842
Notes
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Reaction equation

HRID 1949842 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]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 24386Thionyl ChlorideHCID 568341569-Cyano-4,5-dihydro-6-oxa-1-thia-benzo[e]azulene-2-carboxylic acidHCID 579002073-chloro-N-methyl-4-methylamino-benzamide

Product 1

HCID 57900333N-(2-chloro-4-(methylcarbamoyl)phenyl)-9-cyano-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 6342AcetonitrileSolvent

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

  1. temperatureAfter cooling to room temperature
  2. extractionthe product extracted into ethyl acetate (2×20 mL)
  3. dry with materialThe organics were dried (MgSO4)
  4. 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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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes