Triethylamine → HCID 10411742, compound

HRID 1110206Notes

Reaction equation

HRID 1110206 reaction equation
[CH3:1][N:2]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[C:6]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[N:5][C@@H:4]([NH:19][C:20]([O:22]C2C=CC([N+]([O-])=O)=CC=2)=O)[C:3]1=[O:32].[CH3:33][O:34][C:35](=[O:44])[CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[C:39]([NH2:43])[CH:38]=1.C(N(CC)CC)C>C1COCC1>[CH3:33][O:34][C:35](=[O:44])[CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[C:39]([NH:43][C:20]([NH:19][C@@H:4]2[N:5]=[C:6]([C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:7]3[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=3[N:2]([CH3:1])[C:3]2=[O:32])=[O:22])[CH:38]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 9980117HCID 9980117, compoundHCID 13054266Methyl 3-aminophenylacetate

Product 1

HCID 10411742HCID 10411742, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

(R)-1,3-Dihydro-1-methyl-3-(p-nitrophenyloxycarbonyl)amino-5-phenyl-2H-1,4-benzodiazepin-2-one (1.92 g, 4.47 mmol) was dissolved in THF (25 ml) and treated with a solution of (3-aminophenyl)acetic acid methyl ester (670 mg, 4.06 mmol) in THF (5 ml) followed by triethylamine (615 mg, 6.09 mmol). The mixture was stirred at ambient temperature for 4 days. The solvent was removed in vacuo and the residue was treated with water (20 ml) and extracted with ethyl acetate. The combined ethyl acetate layers were washed with 1M NaOH, then with 10% citric acid, dried over sodium sulfate, filtered and evaporated to dryness in vacuo. The residue was chromatographed on silica gel eluted with 1:1 hexane:ethyl acetate. The product fractions were combined and evaporated to dryness in vacuo and the residue crystallized from ethyl acetate to give (R)-3-((((2,3-Dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4-benzodiazepin-3-yl)amino)carbonyl)amino)phenyl acetic acid methyl ester. This ester (885mg, 1.94mmol) was dissolved in THF (5 ml) and treated with a solution of lithium hydroxide (815 mg, 19.4 mmol) in water (10 ml). The mixture was stirred at ambient temperature for 3 hours, diluted with water (100 ml), acidified with 1N HCl, and extracted with ethyl acetate. The ethyl acetate layers were washed with brine, dried over sodium sulfate, filterate, and evaporated to dryness in vacuo. The residue was chromatographed on silica gel eluted with chloroform followed by 9:1 chloroform:methanol. The product fractions were combined and evaporated to dryness in vacuo. The residue was crystallized from ethyl acetate to provide the title compound: (mp 167°-170° C.).

Workup

  1. customThe solvent was removed in vacuo
  2. additionthe residue was treated with water (20 ml)
  3. extractionextracted with ethyl acetate
  4. washThe combined ethyl acetate layers were washed with 1M NaOH
  5. dry with materialwith 10% citric acid, dried over sodium sulfate
  6. filtrationfiltered
  7. customevaporated to dryness in vacuo
  8. customThe residue was chromatographed on silica gel
  9. washeluted with 1:1 hexane
  10. customevaporated to dryness in vacuo
  11. customthe residue crystallized from ethyl acetate

Sources & evidence

ORD record
ord-b663b2d917e842c3859a827aa626dbde
Source dataset
uspto-grants-1994_06
Patent number
US05324726

Reaction notes

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