3-Amino-1,2-propanediol → 1-[(S)-6-bromo-5-(o-chlorophenyl)-2,3-dihydro-1,3-dimethyl-2-oxo-1H-1,4-benzodiazepin-7-yl]-3-[(2,2-dimethyl-1,3-dioxolan-4-yl)methyl]urea

HRID 1632174Notes

Reaction equation

HRID 1632174 reaction equation
[Br:1][C:2]1[C:7]2[C:8]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[Cl:22])=[N:9][C@@H:10]([CH3:15])[C:11](=[O:14])[N:12]([CH3:13])[C:6]=2[CH:5]=[CH:4][C:3]=1[N:23]=[C:24]=[O:25].N[C:27]1[CH:28]=CC2N(C)C(=O)[C@H](C)N=C(C3C=CC=CC=3Cl)C=2[C:47]=1Br.[NH2:49][CH2:50][CH:51]([OH:54])[CH2:52][OH:53]>CC(C)=O.O>[Br:1][C:2]1[C:7]2[C:8]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[Cl:22])=[N:9][C@@H:10]([CH3:15])[C:11](=[O:14])[N:12]([CH3:13])[C:6]=2[CH:5]=[CH:4][C:3]=1[NH:23][C:24]([NH:49][CH2:50][CH:51]1[CH2:52][O:53][C:27]([CH3:28])([CH3:47])[O:54]1)=[O:25]

Participants

6

Reactant 3

HCID 735613-Amino-1,2-propanediolHCID 53715566(S)-[6-bromo-5-(o-chlorophenyl)-2,3-dihydro-1,3-dimethyl-2-oxo-1H-1,4-benzodiazepin-7-yl]isocyanateHCID 53936752(S)-7-amino-6-bromo-5-(o-chlorophenyl)-1,3-dihydro-1,3-dimethyl-2H-1,4-benzodiazepin-2-one

Product 1

HCID 543347131-[(S)-6-bromo-5-(o-chlorophenyl)-2,3-dihydro-1,3-dimethyl-2-oxo-1H-1,4-benzodiazepin-7-yl]-3-[(2,2-dimethyl-1,3-dioxolan-4-yl)methyl]urea

Reagents, catalysts & solvents 2

HCID 180AcetoneSolvent2×HCID 962WaterSolvent

Procedure

A solution of (S)-[6-bromo-5-(o-chlorophenyl)-2,3-dihydro-1,3-dimethyl-2-oxo-1H-1,4-benzodiazepin-7-yl]isocyanate [obtained in accordance with details in Example 1(f) from 4 g (0.01 mol) of (S)-7-amino-6-bromo-5-(o-chlorophenyl)-1,3-dihydro-1,3-dimethyl-2H-1,4-benzodiazepin-2-one] in acetone is treated with a solution of 3.8 g (0.04 mol) of 3-amino-1,2-propanediol in 10 ml of water and 50 ml of acetone, the mixture is stirred at room temperature for 12 hours and extracted with methylene chloride. The organic extract is dried over sodium sulphate and evaporated, whereupon the residue is chromatographed on silica gel while eluting with chloroform. There is obtained 1-[(S)-6-bromo-5-(o-chlorophenyl)-2,3-dihydro-1,3-dimethyl-2-oxo-1H-1,4-benzodiazepin-7-yl]-3-[(2,2-dimethyl-1,3-dioxolan-4-yl)methyl]urea of melting point 135° (decomposition); [α]25D =+7.6° (0.8 percent solution in methanol).

Workup

  1. extractionextracted with methylene chloride
  2. extractionThe organic extract
  3. dry with materialis dried over sodium sulphate
  4. customevaporated, whereupon the residue
  5. customis chromatographed on silica gel
  6. washwhile eluting with chloroform

Sources & evidence

ORD record
ord-4866b5f706aa405695d8bd3c8f00db3c
Source dataset
uspto-grants-1984_10
Patent number
US04474777

Reaction notes

Loading…