Sodium Carbonate → HCID 57642345, compound

HRID 2112490Notes

Reaction equation

HRID 2112490 reaction equation
[Br:1][C:2]1[C:3]([OH:21])=[CH:4][C:5]2[NH:11][C:10](=[O:12])[CH2:9][N:8]=[C:7]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[Cl:19])[C:6]=2[CH:20]=1.C(=O)([O-])[O-].[Na+].[Na+].Cl[CH2:29][CH2:30][CH2:31][N:32]1[CH2:37][CH2:36][O:35][CH2:34][CH2:33]1>CN(C)C=O>[Br:1][C:2]1[C:3]([O:21][CH2:29][CH2:30][CH2:31][N:32]2[CH2:37][CH2:36][O:35][CH2:34][CH2:33]2)=[CH:4][C:5]2[NH:11][C:10](=[O:12])[CH2:9][N:8]=[C:7]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[Cl:19])[C:6]=2[CH:20]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 958344-(3-Chloropropyl)morpholineHCID 136016305HCID 136016305, compound

Product 1

HCID 57642345HCID 57642345, compoundYield 69.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of 1.8281 g (0.005 mole) of 7-bromo-5-(2-chlorophenyl)-1,3-dihydro-8-hydroxy-2H-1,4-benzodiazepin-2-one (Ipp) from the previous step, 0.636 g of sodium carbonate, 0.9818 g (0.006 mole) of 4-(3-chloropropyl)-morpholine and 50 mL of dimethylformamide was stirred at 50° C., under an argon atmosphere for 73 hours. The mixture was then cooled and partitioned between ethyl acetate and saturated sodium bicarbonate. The aqueous layer was then reextracted with ethyl acetate. The ethyl acetate layers were washed successively with saturated sodium bicarbonate, water, brine and then dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give the crude 7-bromo-5-(2-chlorophenyl)-1,3-dihydro-8-(3-(4-morpholinyl)propoxy)-2H-1,4-benzodiazepin-2-one (Ij). Pure 7-bromo-5-(2-chlorophenyl)-1,3-dihydro-8-(3-(4-morpholinyl)propoxy)-2H-1,4-benzodiazepin-2-one (Ij) (1.721 g) was obtained by silica gel chromatography eluting with ethyl acetate-methanol (90:10). MH+/Z=492.

Workup

  1. temperatureThe mixture was then cooled
  2. custompartitioned between ethyl acetate and saturated sodium bicarbonate
  3. washThe ethyl acetate layers were washed successively with saturated sodium bicarbonate, water, brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customto give the crude 7-bromo-5-(2-chlorophenyl)-1,3-dihydro-8-(3-(4-morpholinyl)propoxy)-2H-1,4-benzodiazepin-2-one (Ij)

Sources & evidence

ORD record
ord-a561fee74061458cb64e3e400c18ee15
Source dataset
uspto-grants-2009_04
Patent number
US07524840B2

Reaction notes

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