Sodium Chloride → HCID 68432201, compound

HRID 1867417Notes

Reaction equation

HRID 1867417 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4](/[CH:9]=[CH:10]/[C:11]([N:13]2[CH2:19][CH2:18][C:17](=[O:20])[N:16]([CH2:21][CH2:22][CH2:23][CH2:24]I)[CH2:15][CH2:14]2)=[O:12])[CH:5]=[CH:6][C:7]=1[Cl:8].[CH3:26][NH:27][CH:28]1[CH2:33][CH2:32][O:31][CH2:30][CH2:29]1.Cl.CNC1CCOCC1.CCN(CC)CC.[Na+].[Cl-]>CC(N(C)C)=O.C1(C)C=CC=CC=1.[OH-].[Na+].C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4](/[CH:9]=[CH:10]/[C:11]([N:13]2[CH2:19][CH2:18][C:17](=[O:20])[N:16]([CH2:21][CH2:22][CH2:23][CH2:24][N:27]([CH3:26])[CH:28]3[CH2:33][CH2:32][O:31][CH2:30][CH2:29]3)[CH2:15][CH2:14]2)=[O:12])[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

10

Reactant 5

HCID 5234Sodium ChlorideHCID 8471TriethylamineHCID 69919504-(Methylamino)tetrahydro-2H-pyran3×HCID 22736998N-methyloxan-4-amine hydrochlorideHCID 68433016HCID 68433016, compound

Product 1

HCID 68432201HCID 68432201, compoundYield 4%

Reagents, catalysts & solvents 4

HCID 1140TolueneSolventHCID 6344DichloromethaneSolventHCID 14798Sodium HydroxideSolvent2×HCID 31374DimethylacetamideSolvent

Procedure

A solution of 0.100 g (0.20 mmol) of 1-[(E)-3-(3,4-dichloro-phenyl)-acryloyl]-4-(4-iodo-butyl)-[1,4]diazepan-5-one (example 9B) in 3.1 ml of DMA was treated with free methyl-(tetrahydro-pyran-4-yl)-amine in 1 ml of toluene [0.035 g (0.22 mmol) methyl-(tetrahydro-pyran-4-yl)-amine hydrochloride were dissolved in 0.8 ml of 0.5 N NaOH was extracted with toluene (2 ml). The organic phase was dried over Na2SO4] and stirred for 22 h at RT, 0.06 ml (0.40 mmol) of Et3N was added and stirring was continued for 18 h at 50° C. Again methyl-(tetrahydro-pyran-4-yl)-amine in 1 ml of CH2Cl2 [0.035 g (0.22 mmol) methyl-(tetrahydro-pyran-4-yl)-amine hydrochloridewere dissolved in 0.5 ml aqueous 10% NaCl solution/0.4 ml of 1 N NaOH was extracted with CH2Cl2 (1 ml). The organic phase was dried over Na2SO4] was added and heated for 9 h at 50° C. The reaction was extracted with aqueous saturated NaHCO3/Et2O (3×). The organic phases were washed with aqueous 10% NaCl, dried (Na2SO4), concentrated and evaporated. Purification by catridges, Si-Amine, 70 ml, 20 g (n-heptane/EtOAc 1:4 to 1:9) gave 0.004 g (4%) of the title compound as a light yellow semisolid. MS: 482.3 (MH+, 2Cl).

Workup

  1. extractionwas extracted with toluene (2 ml)
  2. dry with materialThe organic phase was dried over Na2SO4] and
  3. stirringstirring
  4. waitwas continued for 18 h at 50° C
  5. extractionwas extracted with CH2Cl2 (1 ml)
  6. dry with materialThe organic phase was dried over Na2SO4]
  7. additionwas added
  8. temperatureheated for 9 h at 50° C
  9. extractionThe reaction was extracted with aqueous saturated NaHCO3/Et2O (3×)
  10. washThe organic phases were washed with aqueous 10% NaCl
  11. dry with materialdried (Na2SO4)
  12. concentrationconcentrated
  13. customevaporated
  14. customPurification by catridges, Si-Amine, 70 ml, 20 g (n-heptane/EtOAc 1:4 to 1:9)

Sources & evidence

ORD record
ord-ee4535f1353644dd899932844f6a0895
Source dataset
uspto-grants-2009_12
Patent number
US07632829B2

Reaction notes

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