Methanol → HCID 18677067, compound

HRID 1634053Notes

Reaction equation

HRID 1634053 reaction equation
C[O:2][C:3](=[O:26])[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][N:9]1[C:15](=[O:16])[C:14]2[CH:17]=[C:18]([NH:21][C:22](=[O:24])C)[CH:19]=[CH:20][C:13]=2[NH:12][C:11](=[O:25])[CH2:10]1.CO.O=S(Cl)Cl.[CH2:33]([N:40]=C=O)[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1>CO.Cl>[CH2:33]([NH:40][C:22](=[O:24])[NH:21][C:18]1[CH:19]=[CH:20][C:13]2[NH:12][C:11](=[O:25])[CH2:10][N:9]([CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][C:3]([OH:2])=[O:26])[C:15](=[O:16])[C:14]=2[CH:17]=1)[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 24386Thionyl ChlorideHCID 76639Benzyl isocyanateHCID 69999615HCID 69999615, compound

Product 1

HCID 18677067HCID 18677067, compoundYield 19.5%

Reagents, catalysts & solvents 1

HCID 21893726Hydrochloride methanolSolvent

Procedure

80 mg (0.22 mmol) 6-(7-acetylamino-2,5-dioxo-1,2,3,5-tetrahydro-benzo[e][1,4]diazepin-4-yl)-hexanoic acid methyl ester was dissolved in 1 ml MeOH/HCl (freshly prepared from 10 ml MeOH and 1 ml SOCl2). The solution was stirred for 18 h and concentrated in vacuo. The residue was taken up in 2 ml of THF/MeOH (1: 1) and 0.5 ml 1N aqueous NaOH was added. After stirring for 16 h at 22° C. the mixture was neutralised by addition of solid carbon dioxide, and the solvents were evaporated. The residue was taken up in DMF (2.5 ml) and 0.032 ml benzylisocyanate (0.26 mmol) was added. The mixture was shaken at 45° C. over night and evaporated. The crude product was purified by preparative HPLC to give 6-[7-(3-benzyl-ureido) -2,5-dioxo-1,2,3,5-tetrahydro-benzo[e][1,4]diazepin-4-yl]-hexanoic acid (19 mg, 0.043 mmol): MS (ISN) 437(M−H)−.

Workup

  1. concentrationconcentrated in vacuo
  2. addition0.5 ml 1N aqueous NaOH was added
  3. stirringAfter stirring for 16 h at 22° C. the mixture
  4. additionwas neutralised by addition of solid carbon dioxide
  5. customthe solvents were evaporated
  6. stirringThe mixture was shaken at 45° C. over night
  7. customevaporated
  8. customThe crude product was purified by preparative HPLC

Sources & evidence

ORD record
ord-4a35bf9d3dce46f3bfc1ed9172a6b4d9
Source dataset
uspto-grants-2003_01
Patent number
US06506744B1

Reaction notes

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