Pyridine → N2-(2-chlorophenyl)-N2,N8,N8-trimethyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,8-dicarboxamide

HRID 1949673Notes

Reaction equation

HRID 1949673 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]([CH3:28])[C:9]([C:11]1[S:27][C:14]2[C:15]3[CH:23]=[CH:22][C:21]([C:24](O)=[O:25])=[CH:20][C:16]=3[O:17][CH2:18][CH2:19][C:13]=2[CH:12]=1)=[O:10].[NH:29]([CH3:31])[CH3:30].Cl.N1C=CC=CC=1.ClC1C=CC=CC=1N(C)C(C1SC2C3C=CC(C(Cl)=O)=CC=3OCCC=2C=1)=O>O=S(Cl)Cl.C1COCC1>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]([CH3:28])[C:9]([C:11]1[S:27][C:14]2[C:15]3[CH:23]=[CH:22][C:21]([C:24]([N:29]([CH3:31])[CH3:30])=[O:25])=[CH:20][C:16]=3[O:17][CH2:18][CH2:19][C:13]=2[CH:12]=1)=[O:10]

Participants

7

Reactant 4

HCID 1049PyridineHCID 10473Dimethylamine, hydrochlorideHCID 568340542-((2-Chlorophenyl)(methyl)carbamoyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxylic acidHCID 568340552-((2-Chlorophenyl)(methyl)carbamoyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carbonyl chloride

Product 1

HCID 44224228N2-(2-chlorophenyl)-N2,N8,N8-trimethyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,8-dicarboxamideYield 330.7%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 24386Thionyl ChlorideSolvent

Procedure

Alternatively, a solution of 2-((2-chlorophenyl)(methyl)carbamoyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxylic acid (100 mg, 0.24 mmol) in 2 mL of SOCl2 was heated at 80° C. for 2 h. After removal of the solvent, the residue was co-evaporated with toluene to give the crude acid chloride 2-((2-chlorophenyl)(methyl)carbamoyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carbonyl chloride. To a solution of (CH3)2NH HCl salt (118 mg, 1.412 mmol) and pyridine (0.2 mL) in 5 mL of THF was slowly added 2-((2-chlorophenyl)(methyl)carbamoyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carbonyl chloride (417 mg, 0.966 mmol) in 20 mL of THF. The mixture was stirred at room temperature overnight, concentrated in vacuo, dissolved in ethyl acetate, washed with water and brine, dried over Na2SO4, and concentrated to give 101 (350 mg, yield: 82%). 1H NMR (CDCl3, 400 MHz): δ 6.67-7.59 (m, 8H), 4.16 (t, J=4.8 Hz, 2H), 3.33 (s, 1H), 2.95-2.97 (m, 8H). MS (ESI): 441.1

Workup

  1. customAfter removal of the solvent
  2. customto give the crude acid chloride 2-((2-chlorophenyl)(methyl)carbamoyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carbonyl chloride
  3. concentrationconcentrated in vacuo
  4. dissolutiondissolved in ethyl acetate
  5. washwashed with water and brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-c7aa15ecac174b7586ae263413aca21d
Source dataset
uspto-grants-2013_03
Patent number
US08399690B2

Reaction notes

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