Hydrochloric Acid → HCID 12136496, compound

HRID 2374799Notes

Reaction equation

HRID 2374799 reaction equation
CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C([O:27][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)(C)(C)C.[NH:69]1[CH2:78][CH2:77][CH:72]([C:73]([O:75]C)=[O:74])[CH2:71][CH2:70]1.CCN(C(C)C)C(C)C.Cl>CN(C=O)C.C(Cl)Cl.C(Cl)Cl>[Cl:53][C:48]1[CH:47]=[C:46]([N:45]2[C:41]3=[N:40][CH:39]=[C:38]([S:35]([N:31]4[CH2:32][CH2:33][CH2:34][C@H:30]4[C:28]([N:69]4[CH2:78][CH2:77][CH:72]([C:73]([OH:75])=[O:74])[CH2:71][CH2:70]4)=[O:27])(=[O:36])=[O:37])[N:42]3[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]2=[O:54])[CH:51]=[C:50]([Cl:52])[CH:49]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 424914Methyl isonipecotateHCID 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 12136496HCID 12136496, compoundYield 61.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 22350042dichloromethane N,N-dimethylformamideSolvent

Conditions

Temperature
95 °C

Procedure

TBTU (0.12 g), (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 (Example 14) (0.15 g) and methyl isonipecotate (0.041 g), followed by DIPEA (0.10 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, and extracted with CH2Cl2. The combined organic layers were washed with saturated aqueous NaHCO3 followed by H2O. The organic phase was dried (Na2SO4), filtered and concentrated. The resultant residue was re-dissolved in 30% HBr—AcOH and heated to 95° C. for 3 h. Following aqueous workup, the organic layer was dried (Na2SO4), filtered, concentrated, and the residue was purified by silica gel chromatography to afford the title compound (0.099 g) (738.2, M+1).

Workup

  1. extractionextracted with CH2Cl2
  2. washThe combined organic layers were washed with saturated aqueous NaHCO3
  3. dry with materialThe organic phase was dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. dissolutionThe resultant residue was re-dissolved in 30% HBr—AcOH
  7. dry with materialFollowing aqueous workup, the organic layer was dried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customthe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-cd2ae17db0464d98b49ff713faa1b52d
Source dataset
uspto-grants-2008_12
Patent number
US07462637B2

Reaction notes

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