Chlorodiphenylmethane → N-(2-diphenylmethylamino-5-iodobenzoyl)-b-alanine ethyl ester

HRID 1488667Notes

Reaction equation

HRID 1488667 reaction equation
[CH2:1]([O:3][C:4](=[O:18])[CH2:5][CH2:6][NH:7][C:8](=[O:17])[C:9]1[CH:14]=[C:13]([I:15])[CH:12]=[CH:11][C:10]=1[NH2:16])[CH3:2].FC(F)(F)C(O)=O.CN1C2C=CC(C#CCCCN)=CC=2C(=O)N(CCC(O)=O)CC1=O.N1C(C)=CC=CC=1C.Cl[CH:60]([C:67]1[CH:72]=[CH:71][CH:70]=[CH:69][CH:68]=1)[C:61]1[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=1>CN(C)C=O>[CH2:1]([O:3][C:4](=[O:18])[CH2:5][CH2:6][NH:7][C:8](=[O:17])[C:9]1[CH:14]=[C:13]([I:15])[CH:12]=[CH:11][C:10]=1[NH:16][CH:60]([C:61]1[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=1)[C:67]1[CH:72]=[CH:71][CH:70]=[CH:69][CH:68]=1)[CH3:2]

Participants

6

Reactant 4

HCID 7035ChlorodiphenylmethaneHCID 79372,6-LutidineHCID 10861356N-(2-amino-5-iodobenzoyl)-b-alanine ethyl esterHCID 229051171-methyl-4-(2-carboxyethyl)-7-(5-amino-1-pentynyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione trifluoracetate

Product 1

HCID 22905034N-(2-diphenylmethylamino-5-iodobenzoyl)-b-alanine ethyl esterYield 56.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

A magnetically stirred solution of 1.1 gram of N-(2-amino-5-iodobenzoyl)-b-alanine ethyl ester (3.1 mmol), prepared by the method shown in part (b) of Example 1, 0.48 mL of 2,6-lutidine (4.1 mmol), 1.2 grams of chlorodiphenylmethane (4.7 mmol), and 10 mL of dimethylformamide was heated to 50° C. for 1 hour. The reaction mixture was allowed to cool to room temperature and concentrated in vacuo. The resulting oil was dissolved in 35 mL of methylene chloride and washed with 2×50 mL 10% citric acid, 1×50 mL water, dried over sodium sulfate, decanted and concentrated in vacuo. The resulting oil was further purified by column chromatography, using silica gel, eluting with a solvent gradient of 10/90 ethyl acetate/hexane to 25/75 ethyl acetate/hexane (TLC, SiO2, 1:1 EtOAc/hexane, Rf =0.82, uv positive) to yield 0.92 gram (56%) of N-(2-diphenylmethylamino-5-iodobenzoyl)-b-alanine ethyl ester. 1H NMR (CDCl3, dTMS) 8.40 (1H, d, 3JHH =5 Hz, NHCHAr2), 7.56 (1H, d, 3JHH =2Hz, ArH o-CON), 7.18-7.36 (11H, m, 4 JHH =2 Hz, ArH Ph, ArH p-CON), 6.73 (1H, t, 3JHH =6 Hz, NHCH2), 6.29 (1H, d, 3JHH =9 Hz, ArH m-CON), 5.52 (1H, d, 3JHH =5 Hz, CHNH), 4.15 (2H, q, 3JHH =7 Hz, OCH2), 3.61 (2H, q, 3JHH =6 Hz, CH2NH), 2.58 (2H, t, 3JHH =6 Hz, CH2CO), 1.25 (3H, t, 3JHH =6 Hz, CH3CH2O).

Workup

  1. temperatureto cool to room temperature
  2. concentrationconcentrated in vacuo
  3. dissolutionThe resulting oil was dissolved in 35 mL of methylene chloride
  4. washwashed with 2×50 mL 10% citric acid, 1×50 mL water
  5. dry with materialdried over sodium sulfate
  6. customdecanted
  7. concentrationconcentrated in vacuo
  8. customThe resulting oil was further purified by column chromatography
  9. washeluting with a solvent gradient of 10/90 ethyl acetate/hexane to 25/75 ethyl acetate/hexane (TLC, SiO2, 1:1 EtOAc/hexane, Rf =0.82, uv positive)

Sources & evidence

ORD record
ord-6300e05e020b4cb2a55b68d4830934db
Source dataset
uspto-grants-1997_10
Patent number
US05674865

Reaction notes

Loading…