Diisopropylethylamine → (S)-1-[(R)-5-(4-cyano-benzyl)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-sulfonyl]-pyrrolidine-2-carboxylic acid carbamoylmethyl-amide

HRID 2374795Notes

Reaction equation

HRID 2374795 reaction equation
[C:1]([C:3]1[CH:43]=[CH:42][C:6]([CH2:7][C@@:8]2([CH3:41])[N:12]3[C:13]([S:16]([N:19]4[CH2:23][CH2:22][CH2:21][C@H:20]4[C:24]([NH:26][C@H:27](C)[C:28](O)=[O:29])=[O:25])(=[O:18])=[O:17])=[CH:14][N:15]=[C:11]3[N:10]([C:32]3[CH:37]=[C:36]([Cl:38])[CH:35]=[C:34]([Cl:39])[CH:33]=3)[C:9]2=[O:40])=[CH:5][CH:4]=1)#[N:2].Cl.[NH2:45]CC(N)=O.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CCN(C(C)C)C(C)C>C(Cl)Cl.CN(C=O)C>[C:28]([CH2:27][NH:26][C:24]([C@@H:20]1[CH2:21][CH2:22][CH2:23][N:19]1[S:16]([C:13]1[N:12]2[C@@:8]([CH2:7][C:6]3[CH:5]=[CH:4][C:3]([C:1]#[N:2])=[CH:43][CH:42]=3)([CH3:41])[C:9](=[O:40])[N:10]([C:32]3[CH:33]=[C:34]([Cl:39])[CH:35]=[C:36]([Cl:38])[CH:37]=3)[C:11]2=[N:15][CH:14]=1)(=[O:17])=[O:18])=[O:25])(=[O:29])[NH2:45]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2723639Glycinamide hydrochlorideHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 12136436(R)-2-({(S)-1-[(R)-5-(4-cyano-benzyl)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-sulfonyl]-pyrrolidine-2-carbonyl}-amino)-propionic acid

Product 1

HCID 10009183(S)-1-[(R)-5-(4-cyano-benzyl)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-sulfonyl]-pyrrolidine-2-carboxylic acid carbamoylmethyl-amideYield 56.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

(S)-1-[(R)-5-(4-Cyano-benzyl)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-sulfonyl]-pyrrolidine-2-carboxylic acid (see Example 5) (0.25 g, 0.435 mmol) was dissolved in a mixture of CH2Cl2 (10 mL) and DMF (0.2 mL). To this solution, were added glycinamide hydrochloride (0.072 g, 0.653 mmol), TBTU (0.21 g, 0.653 mmol), and DIPEA (0.19 mL, 1.087 mmol). The reaction mixture was stirred at room temperature for 1 h. The reaction mixture was diluted with CH2Cl2 and washed with 1N HCl followed by saturated aq. NaHCO3. The organic phase was dried over Na2SO4 and concentrated. The crude product was purified by silica gel preparative thin layer chromatography using CH2Cl2-MeOH (95:5) as an eluent to afford 0.155 g of the title compound as a white foam (M+1, 630).

Workup

  1. washwashed with 1N HCl
  2. dry with materialThe organic phase was dried over Na2SO4
  3. concentrationconcentrated
  4. customThe crude product was purified by silica gel preparative thin layer chromatography

Sources & evidence

ORD record
ord-5f2d3856c0f54641addb66245ea84cd6
Source dataset
uspto-grants-2008_12
Patent number
US07462637B2

Reaction notes

Loading…