1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → benzyl N-[(6S,8R)-4-oxo-6-[[4-(N-phenylmethoxycarbonylcarbamimidoyl)phenyl]methylcarbamoyl]-8-prop-2-enyl-7,8-dihydro-6H-pyrrolo[1,2-a]pyrimidin-3-yl]-N-prop-2-enylcarbamate

HRID 10991

Reaction equation

HRID 10991 reaction equation
[CH2:1]([C@H:4]1[C:8]2=[N:9][CH:10]=[C:11]([N:14]([CH2:25][CH:26]=[CH2:27])[C:15]([O:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)=[O:16])[C:12](=[O:13])[N:7]2[C@H:6]([C:28](O)=[O:29])[CH2:5]1)[CH:2]=[CH2:3].Cl.[CH2:32]([O:39][C:40](=[O:52])[NH:41][C:42]([C:44]1[CH:49]=[CH:48][C:47]([CH2:50][NH2:51])=[CH:46][CH:45]=1)=[NH:43])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.C1C=NC2N(O)N=NC=2C=1.C([O-])(O)=O.[Na+].CCN=C=NCCCN(C)C>C(Cl)Cl.CN(C=O)C.CCOC(C)=O>[CH2:25]([N:14]([C:11]1[C:12](=[O:13])[N:7]2[C@H:6]([C:28](=[O:29])[NH:51][CH2:50][C:47]3[CH:46]=[CH:45][C:44]([C:42]([NH:41][C:40]([O:39][CH2:32][C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=4)=[O:52])=[NH:43])=[CH:49][CH:48]=3)[CH2:5][C@@H:4]([CH2:1][CH:2]=[CH2:3])[C:8]2=[N:9][CH:10]=1)[C:15](=[O:16])[O:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[CH:26]=[CH2:27]

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 181649HOAtHCID 516892Sodium BicarbonateHCID 57444828(6S,8R)-8-allyl-3-(allyl-benzyloxycarbonyl-amino)-4-oxo-4,6,7,8-tetrahydro-pyrrolo[1,2-a]pyrimidine-6-carboxylic AcidHCID 145832047Benzyl ((4-(aminomethyl)phenyl)(imino)methyl)carbamate hydrochloride

Product 1

HCID 145857219benzyl N-[(6S,8R)-4-oxo-6-[[4-(N-phenylmethoxycarbonylcarbamimidoyl)phenyl]methylcarbamoyl]-8-prop-2-enyl-7,8-dihydro-6H-pyrrolo[1,2-a]pyrimidin-3-yl]-N-prop-2-enylcarbamateYield 20.8%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

To a solution of 28d (172 mg, 0.420 mmol) and [(4-aminomethyl-phenyl)-imino-methyl]-carbamic acid benzyl ester hydrochloride (180 mg, 0.504 mmol) in 3.6 mL CH2Cl2/DMF (5:1) at 0° C., was added HOAT (113 mg, 0.588 mmol), NaHCO3 (141 mg, 1.68 mmol), and EDCI (113 mg, 0.588 mmol). The mixture was allowed to warm to rt and stir for 64 h. The reaction was diluted with EtOAc and the organic phase was washed with H2O, 1N HCl, H2O, and brine. The organic phase was dried (Na2SO4) and concentrated. The residue obtained was purified by flash chromatography (75% EtOAc/hexanes) to afford 59 mg of intermediate 28e.

Workup

  1. washthe organic phase was washed with H2O, 1N HCl, H2O, and brine
  2. dry with materialThe organic phase was dried (Na2SO4)
  3. concentrationconcentrated
  4. customThe residue obtained
  5. customwas purified by flash chromatography (75% EtOAc/hexanes)

Sources & evidence

ORD record
ord-384eab5d229c455fb8dd63aeadcf8621
Source dataset
uspto-grants-2006_08
Patent number
US07094783B2

Linked notes

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