Hydrochloric Acid → (S)-1-[(R)-7(3,5-dichloro-phenyl)-5-methyl-6-oxo-5-(4-pyrimidin-5-yl-benzyl)-6,7-dihydro-5H-imidazo[1,2-alpha]imidazole-3-sulfonyl]-pyrrolidine-2-carboxylic acid (2-methoxy-ethyl)-amide

HRID 23841Notes

Reaction equation

HRID 23841 reaction equation
CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CCN(C(C)C)C(C)C.C(O[C:37]([C@@H:39]1[CH2:43][CH2:42][CH2:41][N:40]1[S:44]([C:47]1[N:51]2[C@:52]([CH3:77])([CH2:64][C:65]3[CH:70]=[CH:69][C:68]([C:71]4[CH:72]=[N:73][CH:74]=[N:75][CH:76]=4)=[CH:67][CH:66]=3)[C:53](=[O:63])[N:54]([C:55]3[CH:60]=[C:59]([Cl:61])[CH:58]=[C:57]([Cl:62])[CH:56]=3)[C:50]2=[N:49][CH:48]=1)(=[O:46])=[O:45])=[O:38])(C)(C)C.[CH3:78][O:79][CH2:80][CH2:81][NH2:82].Cl>CN(C=O)C.C(Cl)Cl.C(Cl)Cl>[CH3:78][O:79][CH2:80][CH2:81][NH:82][C:37]([C@@H:39]1[CH2:43][CH2:42][CH2:41][N:40]1[S:44]([C:47]1[N:51]2[C@:52]([CH3:77])([CH2:64][C:65]3[CH:70]=[CH:69][C:68]([C:71]4[CH:76]=[N:75][CH:74]=[N:73][CH:72]=4)=[CH:67][CH:66]=3)[C:53](=[O:63])[N:54]([C:55]3[CH:56]=[C:57]([Cl:62])[CH:58]=[C:59]([Cl:61])[CH:60]=3)[C:50]2=[N:49][CH:48]=1)(=[O:45])=[O:46])=[O:38]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 80182-MethoxyethylamineHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 12136449(S)-1-[(R)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-5-(4-pyrimidin-5-yl-benzyl)-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-sulfonyl]-pyrrolidine-2-carboxylic acid tert-butyl ester

Product 1

HCID 12136451(S)-1-[(R)-7(3,5-dichloro-phenyl)-5-methyl-6-oxo-5-(4-pyrimidin-5-yl-benzyl)-6,7-dihydro-5H-imidazo[1,2-alpha]imidazole-3-sulfonyl]-pyrrolidine-2-carboxylic acid (2-methoxy-ethyl)-amideYield 44.9%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

TBTU (0.077 g), DIPEA (0.090 mL) and (S)-1-[(R)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-5-(4-pyrimidin-5-yl-benzyl)-6,7-dihydro-5H-imidazo[1,2-α]imidazole-3-sulfonyl]-pyrrolidine-2-carboxylic acid (Example 14) (0.10 g) were combined in 5% DMF-CH2Cl2 (4.2 mL) at room temperature. 2-Methoxyethylamine (0.036 g) was then added and the reaction solution was stirred overnight. The reaction was diluted with CH2Cl2, poured into 1N HCl, and extracted with CH2Cl2. The organic layers were subsequently extracted with CH2Cl2 from saturated aqueous NaHCO3 followed by brine. The combined organic phase was dried (MgSO4), filtered, and concentrated. The residue was purified by silica gel chromatography to afford 0.045 g of the title compound (684.2, M+1) as a foam.

Workup

  1. extractionextracted with CH2Cl2
  2. extractionThe organic layers were subsequently extracted with CH2Cl2 from saturated aqueous NaHCO3
  3. dry with materialThe combined organic phase was dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-79b49aa8c01e40319a213ea51d083c19
Source dataset
uspto-grants-2005_02
Patent number
US06852748B1

Reaction notes

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