1-Chloroethyl chloroformate → 4-[(5S,9R)-3-(3,5-Dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro[4.4]non-9-yl]-benzonitrile

HRID 1792874Notes

Reaction equation

HRID 1792874 reaction equation
ClC(OC(Cl)C)=O.C([N:15]1[CH2:34][C@@H:33]([C:35]2[CH:42]=[CH:41][C:38]([C:39]#[N:40])=[CH:37][CH:36]=2)[C@:17]2([N:21]([CH3:22])[C:20](=[O:23])[N:19]([C:24]3[CH:29]=[C:28]([Cl:30])[CH:27]=[C:26]([Cl:31])[CH:25]=3)[C:18]2=[O:32])[CH2:16]1)C1C=CC=CC=1>C(Cl)Cl>[Cl:31][C:26]1[CH:25]=[C:24]([N:19]2[C:18](=[O:32])[C@@:17]3([C@H:33]([C:35]4[CH:36]=[CH:37][C:38]([C:39]#[N:40])=[CH:41][CH:42]=4)[CH2:34][NH:15][CH2:16]3)[N:21]([CH3:22])[C:20]2=[O:23])[CH:29]=[C:28]([Cl:30])[CH:27]=1

Participants

4

Reactant 2

HCID 5213051-Chloroethyl chloroformateHCID 119945114-[(5S*,9R*)-7-Benzyl-3-(3,5-dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro[4.4]non-9-yl]-benzonitrile

Product 1

HCID 119947544-[(5S,9R)-3-(3,5-Dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro[4.4]non-9-yl]-benzonitrileYield 116.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

1-Chloroethyl chloroformate (4.4 ml, 40.3 mmol) was added to a cooled (5° C.) solution of Example 14 (5.1 g, 10.1 mmol) in DCM (250 ml). After 1 h at 5° C., the reaction mixture was stirred at RT for 20 h. The solution was concentrated to dryness and then refluxed in MeOH (350 ml) for 3 h. After concentration in vacuo, the oily residue was triturated in Et2O to give the hydrochloride of the desired compound (4.9 g). After basification, the product was chromatographed over silica gel (DCM/MeOH 90/10) to yield the above-titled compound (3.35 g) as an amorphous solid. 1H NMR (CDCl3): 7.64 (2H, d, J=8.4 Hz), 7.25–7.32 (3H, m), 6.72 (2H, d, J=2 Hz), 3.6–3.75 (2H, m), 3.35–3.55 (3H, m), 3.20 (3H, s), 2.16 (1H, br s).

Workup

  1. concentrationThe solution was concentrated to dryness
  2. temperaturerefluxed in MeOH (350 ml) for 3 h
  3. concentrationAfter concentration in vacuo
  4. customthe oily residue was triturated in Et2O

Sources & evidence

ORD record
ord-7cb9e9d519f0413c8a1628a32eb49f53
Source dataset
uspto-grants-2006_07
Patent number
US07078420B2

Reaction notes

Loading…