Tetrahydrofuran → N-(2-chloro-4-fluorophenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide

HRID 2078783Notes

Reaction equation

HRID 2078783 reaction equation
[Cl:1][C:2]1[CH:8]=[C:7]([F:9])[CH:6]=[CH:5][C:3]=1[NH2:4].[CH2:10](N(CC)CC)C.O1CCCC1.[S:22]1[C:26]2[C:27]3[CH:35]=[CH:34][CH:33]=[CH:32][C:28]=3[O:29][CH2:30][CH2:31][C:25]=2[CH:24]=[C:23]1[C:36](Cl)=[O:37]>>[Cl:1][C:2]1[CH:8]=[C:7]([F:9])[CH:6]=[CH:5][C:3]=1[N:4]([CH3:10])[C:36]([C:23]1[S:22][C:26]2[C:27]3[CH:35]=[CH:34][CH:33]=[CH:32][C:28]=3[O:29][CH2:30][CH2:31][C:25]=2[CH:24]=1)=[O:37]

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 75013Benzenamine, 2-chloro-4-fluoro-HCID 579001474,5-Dihydrobenzo[b]thieno[2,3-d]oxepine-2-carbonylchloride

Product 1

HCID 57900362N-(2-chloro-4-fluorophenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide

Procedure

To a solution of 2-chloro-4-fluoroaniline (0.110 g, 0.755 mmol) and triethylamine (0.105 mL, 0.755 mmol) in tetrahydrofuran (1.5 mL, 18 mmol) was added portion wise as a solid 4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carbonyl chloride (0.100 g, 0.378 mmol). Reaction mix was stirred at room temperature with monitor for formation of desired product. The reaction was stirred overnight. The mixture containing the alkylated product was concentrated in vacuo to a solid residue, then taken into N,N-dimethylformamide (1.5 mL, 19 mmol) and treated with sodium hydride (0.0181 g, 0.755 mmol) followed by the addition of methyl iodide (0.0470 mL, 0.755 mmol). Reaction stirred at room temperature for about 1 hr with complete conversion to desired N-methyl derivative. After aqueous work up, the crude was taken into DMF at 100 mg/1 mL and purified by preparative RP-HPLC to give 107. Yield=22% of theoretical. MS: (ESI+) 375

Workup

  1. customReaction
  2. additionmix

Sources & evidence

ORD record
ord-68c0190626ef4262b6c1f2e6cd2b4b27
Source dataset
uspto-grants-2011_04
Patent number
US07928248B2

Reaction notes

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