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 489239Notes

Reaction equation

HRID 489239 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-9e6ffcb958b54bd9bfc1c2e073ca539d
Source dataset
uspto-grants-2005_12
Patent number
US06977267B2

Reaction notes

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