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-carbamoyl-ethyl)-amide

HRID 23843Notes

Reaction equation

HRID 23843 reaction equation
C[N:2](C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(O[C:28]([C@@H:30]1[CH2:34][CH2:33][CH2:32][N:31]1[S:35]([C:38]1[N:42]2[C@:43]([CH3:68])([CH2:55][C:56]3[CH:61]=[CH:60][C:59]([C:62]4[CH:63]=[N:64][CH:65]=[N:66][CH:67]=4)=[CH:58][CH:57]=3)[C:44](=[O:54])[N:45]([C:46]3[CH:51]=[C:50]([Cl:52])[CH:49]=[C:48]([Cl:53])[CH:47]=3)[C:41]2=[N:40][CH:39]=1)(=[O:37])=[O:36])=[O:29])(C)(C)C.C[O:70][C:71](=O)[CH2:72][CH2:73][NH2:74].CCN(C(C)C)C(C)C.Cl>CN(C=O)C.C(Cl)Cl.C(Cl)Cl>[C:71]([CH2:72][CH2:73][NH:74][C:28]([C@@H:30]1[CH2:34][CH2:33][CH2:32][N:31]1[S:35]([C:38]1[N:42]2[C@:43]([CH3:68])([CH2:55][C:56]3[CH:57]=[CH:58][C:59]([C:62]4[CH:63]=[N:64][CH:65]=[N:66][CH:67]=4)=[CH:60][CH:61]=3)[C:44](=[O:54])[N:45]([C:46]3[CH:51]=[C:50]([Cl:52])[CH:49]=[C:48]([Cl:53])[CH:47]=3)[C:41]2=[N:40][CH:39]=1)(=[O:37])=[O:36])=[O:29])(=[O:70])[NH2:2]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 192794Methyl beta-alanateHCID 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 59985285(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-carbamoyl-ethyl)-amideYield 10.3%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 22350042dichloromethane N,N-dimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

TBTU (0.15 g), (S)-1-[(R)-7-(3,5-dichlorophenyl)-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) (0.20 g), β-alanine methyl ester (0.067 g) and DIPEA (0.14 mL) were combined in 1% DMF—CH2Cl2 (10.1 mL) at room temperature and the solution was stirred for 1 h. The reaction was diluted with CH2Cl2, poured into 1N HCl, a nd extracted with CH2Cl2. The organic layers were combined and washed with saturated aqueous NaHCO3 followed by H2O. The combined organic phase was dried (Na2SO4), filtered and concentrated. The resultant residue was re-dissolved in 2N NH3—CH3OH (10 mL) and heated to 40-60° C. for 48 h. The volatiles were removed and the residue was purified by silica gel chromatography to afford the title compound (0.021 g) as a foam (697.2, M+1).

Workup

  1. extractiona nd extracted with CH2Cl2
  2. washwashed with saturated aqueous NaHCO3
  3. dry with materialThe combined organic phase was dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. dissolutionThe resultant residue was re-dissolved in 2N NH3—CH3OH (10 mL)
  7. customThe volatiles were removed
  8. customthe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-3454bb2977494c67b086947b30a1a0df
Source dataset
uspto-grants-2005_02
Patent number
US06852748B1

Reaction notes

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