Diisopropylethylamine → N2-(2-chloro-4-(dimethylcarbamoyl)phenyl)-N2,N8-dimethyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,8-dicarboxamide

HRID 1949783Notes

Reaction equation

HRID 1949783 reaction equation
C[CH2:2][N:3](C(C)C)C(C)C.NC.Cl.[Cl:13][C:14]1[CH:19]=[C:18]([C:20](=[O:24])[N:21]([CH3:23])[CH3:22])[CH:17]=[CH:16][C:15]=1[N:25]([CH3:45])[C:26]([C:28]1[S:44][C:31]2[C:32]3[CH:40]=[CH:39][C:38]([C:41]([OH:43])=O)=[CH:37][C:33]=3[O:34][CH2:35][CH2:36][C:30]=2[CH:29]=1)=[O:27].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C1COCC1>[Cl:13][C:14]1[CH:19]=[C:18]([C:20](=[O:24])[N:21]([CH3:23])[CH3:22])[CH:17]=[CH:16][C:15]=1[N:25]([CH3:45])[C:26]([C:28]1[S:44][C:31]2[C:32]3[CH:40]=[CH:39][C:38]([C:41]([NH:3][CH3:2])=[O:43])=[CH:37][C:33]=3[O:34][CH2:35][CH2:36][C:30]=2[CH:29]=1)=[O:27]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 6364545Methylamine hydrochlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 568342692-((2-Chloro-4-(dimethylcarbamoyl)phenyl)(methyl) carbamoyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxylic acid

Product 1

HCID 53307606N2-(2-chloro-4-(dimethylcarbamoyl)phenyl)-N2,N8-dimethyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2,8-dicarboxamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

DIPEA (16.83 g, 130.2 mmol) was added to a suspension of H2NMe.HCl (5.02 g, 74.4 mmol) in THF (180 mL) and stirred at room temperature for 0.5 h. 2-((2-Chloro-4-(dimethylcarbamoyl)phenyl)(methyl) carbamoyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxylic acid (9.00 g, 18.6 mmol) and HATU (21.22 g, 55.8 mmol) were added into the suspension separately. The reaction mixture was stirred at room temperature for 2 h. Concentrated to remove solvent, the resulting mixture was dissolved in CH2Cl2 (200 mL), washed by 2N HCl (200 mL), water (100 mL), and dried over Na2SO4. The crude product was purified by silica gel chromatography eluted with CH2Cl2:MeOH=10:1 (3.70 g, 40%) to furnish 223. ESI-MS: 498. 1H NMR (CDCl3, 400 MHz): δ7.58 (s, 1H, ArH), 7.42-7.29 (m, 4H, ArH), 6.92 (s, 1H, ArH), 6.34 (d, J=4.0 Hz, 1H, NH), 4.20 (t, J=5.0 Hz, 2H, CH2), 3.37 (s, 3H, CH3), 3.12 (s, 3H, CH3), 3.04-2.98 (m, 8H, CH2, 2CH3).

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 2 h
  2. concentrationConcentrated
  3. customto remove solvent
  4. dissolutionthe resulting mixture was dissolved in CH2Cl2 (200 mL)
  5. washwashed by 2N HCl (200 mL), water (100 mL)
  6. dry with materialdried over Na2SO4
  7. customThe crude product was purified by silica gel chromatography
  8. washeluted with CH2Cl2

Sources & evidence

ORD record
ord-68f8ab90a1124f01b6978265535febb4
Source dataset
uspto-grants-2013_03
Patent number
US08399690B2

Reaction notes

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