Methylamine → Urea, N-(6-chloro-5-(2-fluorophenyl)-2,3-dihydro-1-methyl-2-oxo-1H-1,4-benzodiazepin-7-yl)-N(sup 1)-methyl-

HRID 848121Notes

Reaction equation

HRID 848121 reaction equation
CN.ClC(Cl)C.[Cl:7][C:8]1[C:13]2[C:14]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[F:27])=[N:15][CH2:16][C:17](=[O:20])[N:18]([CH3:19])[C:12]=2[CH:11]=[CH:10][C:9]=1[N:28]=[C:29]=[O:30].[NH2:31][C:32]1C=CC2N(C)C(=O)CN=C(C3C=CC=CC=3F)C=2C=1Cl>>[Cl:7][C:8]1[C:13]2[C:14]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[F:27])=[N:15][CH2:16][C:17](=[O:20])[N:18]([CH3:19])[C:12]=2[CH:11]=[CH:10][C:9]=1[NH:28][C:29]([NH:31][CH3:32])=[O:30]

Participants

5

Reactant 4

HCID 6329MethylamineHCID 63651,1-DichloroethaneHCID 20562329HCID 20562329, compoundHCID 20562334HCID 20562334, compound

Product 1

HCID 3058270Urea, N-(6-chloro-5-(2-fluorophenyl)-2,3-dihydro-1-methyl-2-oxo-1H-1,4-benzodiazepin-7-yl)-N(sup 1)-methyl-

Procedure

Excess gaseous methylamine is conducted into a dichloroethane solution of [6-chloro-5-(o-fluorophenyl)-2,3-dihydro-1-methyl-2-oxo-1H-1,4-benzodiazepin-7-yl]isocyanate, obtained in analogy to the procedure described in paragraph (a) of Example 1 from 10 g (0.031 M) of 7-amino-6-chloro-5-(o-fluorophenyl)-1,3-dihydro-1-methyl-2H-1,4-benzodiazepin-2-one, and the mixture is concentrated. The residue is dissolved in methylene chloride/water and extracted with methylene chloride. The organic phase is separated, dried with sodium sulphate, filtered and concentrated. After purification on a 500 g silica gel column using ethyl acetate as the eluting agent, the product is crystallised from ethyl acetate/ether. There is obtained 1-[6-chloro-5-(o-fluorophenyl)-2,3-dihydro-1-methyl-2-oxo-1H-1,4-benzodiazepin-7-yl]-3-methylurea which melts at 145°-160° C. with decomposition.

Workup

  1. customobtained in analogy to the procedure
  2. concentrationthe mixture is concentrated
  3. dissolutionThe residue is dissolved in methylene chloride/water
  4. extractionextracted with methylene chloride
  5. customThe organic phase is separated
  6. dry with materialdried with sodium sulphate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customAfter purification on a 500 g silica gel column
  10. customthe product is crystallised from ethyl acetate/ether

Sources & evidence

ORD record
ord-c26dc3fdd7e441cbb75e570f7bca50b4
Source dataset
uspto-grants-1981_10
Patent number
US04294758

Reaction notes

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