1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → N-Methyl-N-(tetrahydro-2H-pyran-4-yl)-[2,1,3]-benzothiadiazole-5-carboxamide

HRID 1951033Notes

Reaction equation

HRID 1951033 reaction equation
[CH3:1][NH:2][CH:3]1[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1.[N:9]1[S:10][N:11]=[C:12]2[CH:17]=[C:16]([C:18](O)=[O:19])[CH:15]=[CH:14][C:13]=12.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C>CN(C1C=CN=CC=1)C.CN(C=O)C.C(N(CC)CC)C>[CH3:1][N:2]([CH:3]1[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1)[C:18]([C:16]1[CH:15]=[CH:14][C:13]2=[N:9][S:10][N:11]=[C:12]2[CH:17]=1)=[O:19]

Participants

8

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 6020112,1,3-Benzothiadiazole-5-carboxylic acidHCID 69919504-(Methylamino)tetrahydro-2H-pyran

Product 1

HCID 25104408N-Methyl-N-(tetrahydro-2H-pyran-4-yl)-[2,1,3]-benzothiadiazole-5-carboxamide

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

N-Methyltetrahydro-2H-pyran-4-amine (0.4 g, 3.4 mmol), [2,1,3]-benzothiadiazole-5-carboxylic acid (0.23 g, 1.4 mmol), DMAP (0.2 g: 1.6 mmol), HOBT (0.2 g, 1.5 mmol), triethylamine (1.0 ml) and EDCI (1 g, 6.4 mmol) were dissolved in DMF (30 ml). The mixture was stirred at room temperature for 18 h and then concentrated under vacuum. Chloroform (100 ml) was added and the mixture washed with water (100 ml) and H2SO4 (→pH 2) and NaHCO3 solution (100 ml). The aqueous was extracted with chloroform (100 ml) and the combined organics were dried (MgSO4), concentrated under vacuum, and the crude product was purified on a silica gel column eluting with chloroform/THF (90:10), to give the product as an oil which crystallized on standing. Mp=106-108° C., 1H NMR (300 MHz, CDCl3, rotamers) δ 8.06 (d, J=9.0 Hz, 1H); 8.01 (s, 1H); 7.60 (d, J=9.0 Hz, 1H); 4.92-4.75 and 4.15-3.10 (m, 5H); 3.10-2.80 (m, 3H) and 2.05-1.50 ppm (s, 4H).

Workup

  1. concentrationconcentrated under vacuum
  2. additionChloroform (100 ml) was added
  3. washthe mixture washed with water (100 ml) and H2SO4 (→pH 2) and NaHCO3 solution (100 ml)
  4. extractionThe aqueous was extracted with chloroform (100 ml)
  5. dry with materialthe combined organics were dried (MgSO4)
  6. concentrationconcentrated under vacuum
  7. customthe crude product was purified on a silica gel column
  8. washeluting with chloroform/THF (90:10)

Sources & evidence

ORD record
ord-b504b6d774d149f78f34469d4f530d8b
Source dataset
uspto-grants-2013_03
Patent number
US08404682B2

Reaction notes

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