1,1'-Carbonyldiimidazole → Imidazole-1-carboxylic acid {(R)-1-[9-((1R,2S,3R,4S)-2,3-dihydroxy-4-propionylamino-cyclopentyl)-6-(2,2-diphenyl-ethylamino)-9H-purin-2-yl]-pyrrolidin-3-yl}-amide

HRID 2382413Notes

Reaction equation

HRID 2382413 reaction equation
[NH2:1][C@@H:2]1[CH2:6][CH2:5][N:4]([C:7]2[N:15]=[C:14]3[C:10]([N:11]=[CH:12][N:13]3[C@H:16]3[C@@H:20]4[O:21]C(C)(C)[O:23][C@@H:19]4[C@@H:18]([NH:26][C:27](=[O:30])[CH2:28][CH3:29])[CH2:17]3)=[C:9]([NH:31][CH2:32][CH:33]([C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=3)[C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[N:8]=2)[CH2:3]1.[CH:46]1[N:50]=[CH:49][N:48]([C:51](N2C=NC=C2)=[O:52])[CH:47]=1>C(Cl)Cl>[OH:21][C@@H:20]1[C@H:19]([OH:23])[C@@H:18]([NH:26][C:27](=[O:30])[CH2:28][CH3:29])[CH2:17][C@H:16]1[N:13]1[CH:12]=[N:11][C:10]2[C:14]1=[N:15][C:7]([N:4]1[CH2:5][CH2:6][C@@H:2]([NH:1][C:51]([N:48]3[CH:47]=[CH:46][N:50]=[CH:49]3)=[O:52])[CH2:3]1)=[N:8][C:9]=2[NH:31][CH2:32][CH:33]([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1

Participants

4

Reactant 2

HCID 682631,1'-CarbonyldiimidazoleHCID 66629700N-{(3aR,4S,6R,6aS)-6-[2-((R)-3-amino-pyrrolidin-1-yl)-6-(2,2-diphenyl-ethylamino)-purin-9-yl]-2,2-dimethyl-tetrahydro-cyclopenta[1,3]dioxol-yl}-propionamide2×

Product 1

HCID 66630746Imidazole-1-carboxylic acid {(R)-1-[9-((1R,2S,3R,4S)-2,3-dihydroxy-4-propionylamino-cyclopentyl)-6-(2,2-diphenyl-ethylamino)-9H-purin-2-yl]-pyrrolidin-3-yl}-amide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture comprising N-{(3aR,4S,6R,6aS)-6-[2-((R)-3-amino-pyrrolidin-1-yl)-6-(2,2-diphenyl-ethylamino)-purin-9-yl]-2,2-dimethyl-tetrahydro-cyclopenta[1,3]dioxol-yl}-propionamide (Intermediate M) (0.24 g, 394 μmol) and CDI (0.275 g, 1.7 mmol) in dry DCM (6 ml) is stirred at room temperature for 3 hours. The resulting solution is purified by chromatography on silica eluting with 100% DCM changing to 5% MeOH in DCM to afford the title compound as a yellow oil. The oil consists of the imidazole-urea intermediate together with variable amounts of the corresponding isocyanate and imidazole which are equally suitable as precursors to ureas.

Workup

  1. customThe resulting solution is purified by chromatography on silica eluting with 100% DCM changing to 5% MeOH in DCM

Sources & evidence

ORD record
ord-a61f672701d740ccbb81ae11bd73be9d
Source dataset
uspto-grants-2012_09
Patent number
US08258141B2

Reaction notes

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