Dicyclohexylcarbodiimide → 1,3-Dihydro-5-(2-fluorophenyl)-3(RS)-(2-thienyl)methyl-2H-1,4-benzodiazepin-2-one

HRID 620564Notes

Reaction equation

HRID 620564 reaction equation
[NH2:1][C:2]1[CH:16]=[CH:15][CH:14]=[CH:13][C:3]=1[C:4]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[F:12])=O.C([NH:24][CH:25]([C:32](O)=[O:33])[CH2:26][C:27]1[S:28][CH:29]=[CH:30][CH:31]=1)(OC(C)(C)C)=O.C1CCC(N=C=NC2CCCCC2)CC1>C(Cl)Cl>[F:12][C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=1[C:4]1[C:3]2[CH:13]=[CH:14][CH:15]=[CH:16][C:2]=2[NH:1][C:32](=[O:33])[CH:25]([CH2:26][C:27]2[S:28][CH:29]=[CH:30][CH:31]=2)[N:24]=1

Participants

5

Reactant 3

HCID 10868DicyclohexylcarbodiimideHCID 741012-Amino-2'-fluorobenzophenoneHCID 5035100N-Boc-beta-(2-thienyl)-DL-alanine

Product 1

HCID 156147381,3-Dihydro-5-(2-fluorophenyl)-3(RS)-(2-thienyl)methyl-2H-1,4-benzodiazepin-2-one

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The procedure of Example 1 was carried out using 2-amino-2'-fluorobenzophenone (1.26 gm, 5.86 mmol), N-Boc-β-(2-thienyl)-DL-alanine (1.75 gm, 6.45 mmol), and DCC (6.45 ml of 1.0M solution in CH2Cl2) in CH2Cl2 (25 ml). Filtration, concentration in vacuo and flash chromatography (silica gel, 1% (v/v) Et2O in CH2Cl2) gave a white foam which was deprotected and cyclized by the procedure of Example 2. After stirring 3 days, the mixture was evaporated in vacuo, treated with H2O (50 ml) and extracted with EtOAc (2×100 ml). The combined organic extracts were washed with brine (50 ml), dried over MgSO4, filtered, and evaporated to dryness in vacuo. The resulting foam was crystallized from Et2O to give the title compound as a white solid. The solid was dried in vacuo at 65° C.: (m.p. 189°-91° C.).

Workup

  1. filtrationFiltration, concentration in vacuo and flash chromatography (silica gel, 1% (v/v) Et2O in CH2Cl2)
  2. customgave a white foam which
  3. customthe mixture was evaporated in vacuo
  4. additiontreated with H2O (50 ml)
  5. extractionextracted with EtOAc (2×100 ml)
  6. washThe combined organic extracts were washed with brine (50 ml)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. customevaporated to dryness in vacuo
  10. customThe resulting foam was crystallized from Et2O

Sources & evidence

ORD record
ord-55b7159441b04f349d572dc2bb035ec9
Source dataset
uspto-grants-1989_04
Patent number
US04820834

Reaction notes

Loading…