1,2-Dichloroethane → HCID 70150347, compound

HRID 2268802Notes

Reaction equation

HRID 2268802 reaction equation
CN1CCOCC1.C1C=CC2N(O)N=NC=2C=1.[C:18]([C:21]1[C:22]([C:29]([OH:31])=O)=[C:23]([CH3:28])[N:24]([CH3:27])[C:25]=1[CH3:26])(=[O:20])[CH3:19].C(Cl)CCl.[CH3:36][O:37][C:38](=[O:58])[C@H:39]([CH2:41][C:42]1[CH:47]=[CH:46][C:45]([O:48][CH2:49][C:50]2[C:55]([Cl:56])=[CH:54][CH:53]=[CH:52][C:51]=2[Cl:57])=[CH:44][CH:43]=1)[NH2:40]>CN(C=O)C>[CH3:36][O:37][C:38](=[O:58])[C@H:39]([CH2:41][C:42]1[CH:43]=[CH:44][C:45]([O:48][CH2:49][C:50]2[C:55]([Cl:56])=[CH:54][CH:53]=[CH:52][C:51]=2[Cl:57])=[CH:46][CH:47]=1)[NH:40][C:29]([C:22]1[C:21]([C:18](=[O:20])[CH3:19])=[C:25]([CH3:26])[N:24]([CH3:27])[C:23]=1[CH3:28])=[O:31]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 12167345HCID 12167345, compoundHCID 18332512HCID 18332512, compound

Product 1

HCID 70150347HCID 70150347, compoundYield 51.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

NMM (155 mg, 169 μl, 1.54 mmol), HOBT (227 mg, 1.68 mmol), 4-acetyl-1,2,5-trimethylpyrrole-3-carboxylic acid (300 mg, 1.54 mmol) and EDC (295 mg, 1.54 mmol) were added sequentially to a stirred solution of O-(2,6-dichlorobenzyl)-L-tyrosine methyl ester hydrochloric (546 mg, 1.40 mmol) in dry DMF (15 ml). The reaction was stirred at room temperature under N2 for 18 h. The solvent was removed in vacuo and the residue partitioned between EtOAc (50 ml), and 10%aqueous Na2CO3 (40 ml). The phases were separated and the queous phase extracted with EtOac (2×25 ml). The combined organic extracts were washed consecutively with 5% aqueous hydrochloric acid (20 ml), 10% aqueous Na2SO3 (20 ml) and brine (10 ml), dried (Na2SO4) and evaporated in vacuo. The obtained orange foam (0.6 g) was chromatographed (silica; 50% EtOAc/Hexane→100% EtOAc) affording the title compound as a white foam (380 mg, 51%); 'Hnmr (d6DMSO) 8.53 (1H, d, J 8Hz, NH), 7.57-7.43 (3H, m's, aryl-H), 7.22 (2H, d, J 8.5Hz), aryl-H), 6.95 (2H, d, J 8.5 Hz, aryl-H), 5.18 (2H, br s, CH2-O), 4.67 (1H, m, α-tyr-H), 3.66 (3H, s, Me-O), 3.34 (3H, s, Me-N), 3.12 (1H, dd, J 4.1, 13.8Hz, CHABBAr), 2.90 (1H, dd, J 11.3 13.8Hz, CH2HBAr), 2.32 (3H, s, MeCO), 2.0 (3H, s, pyrrole-Me) and 1.94 (3H, s, pyrrole-Me). m/z (ES+60V) 531 (MH+, 100 ), 533 (MH+, 75) 553( MNz+, 15%).

Workup

  1. customThe solvent was removed in vacuo
  2. customthe residue partitioned between EtOAc (50 ml), and 10%aqueous Na2CO3 (40 ml)
  3. customThe phases were separated
  4. extractionthe queous phase extracted with EtOac (2×25 ml)
  5. washThe combined organic extracts were washed consecutively with 5% aqueous hydrochloric acid (20 ml), 10% aqueous Na2SO3 (20 ml) and brine (10 ml)
  6. dry with materialdried (Na2SO4)
  7. customevaporated in vacuo
  8. customThe obtained orange foam (0.6 g) was chromatographed (silica; 50% EtOAc/Hexane→100% EtOAc)

Sources & evidence

ORD record
ord-d327a3776439444a920e343758727fd7
Source dataset
uspto-grants-2001_12
Patent number
US06329372B1

Reaction notes

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