N-[1-(2-pyridinyl)-4-piperidinyl]-1H-imidazole-1-carboxamide → [(1S,2R,3S,4R)-4-(6-(2,2-Diphenyl-ethylamino)-2-{2-[3-(3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-yl)-ureido]-ethylcarbamoyl}-purin-9-yl)-2,3-dihydroxy-cyclopentyl]-carbamic acid tert-butyl ester

HRID 2382407Notes

Reaction equation

HRID 2382407 reaction equation
[C:1]([O:5][C:6](=[O:45])[NH:7][C@H:8]1[CH2:12][C@@H:11]([N:13]2[CH:21]=[N:20][C:19]3[C:14]2=[N:15][C:16]([C:37](=[O:42])[NH:38][CH2:39][CH2:40][NH2:41])=[N:17][C:18]=3[NH:22][CH2:23][CH:24]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C@H:10]([OH:43])[C@@H:9]1[OH:44])([CH3:4])([CH3:3])[CH3:2].[N:46]1([C:60]2[CH:65]=[CH:64][CH:63]=[CH:62][N:61]=2)[CH2:51][CH2:50][CH:49]([NH:52][C:53](N2C=CN=C2)=[O:54])[CH2:48][CH2:47]1>CC(O)C.C(Cl)Cl>[C:1]([O:5][C:6](=[O:45])[NH:7][C@H:8]1[CH2:12][C@@H:11]([N:13]2[CH:21]=[N:20][C:19]3[C:14]2=[N:15][C:16]([C:37](=[O:42])[NH:38][CH2:39][CH2:40][NH:41][C:53]([NH:52][CH:49]2[CH2:48][CH2:47][N:46]([C:60]4[CH:65]=[CH:64][CH:63]=[CH:62][N:61]=4)[CH2:51][CH2:50]2)=[O:54])=[N:17][C:18]=3[NH:22][CH2:23][CH:24]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C@H:10]([OH:43])[C@@H:9]1[OH:44])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 2

HCID 21978278N-[1-(2-pyridinyl)-4-piperidinyl]-1H-imidazole-1-carboxamide2×HCID 66630888{(1S,2R,3S,4R)-4-[2-(2-Amino-ethylcarbamoyl)-6-(2,2-diphenyl-ethylamino)-purin-9-yl]-2,3-dihydroxy-cyclopentyl}-carbamic acid tert-butyl ester

Product 1

HCID 24863127[(1S,2R,3S,4R)-4-(6-(2,2-Diphenyl-ethylamino)-2-{2-[3-(3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-yl)-ureido]-ethylcarbamoyl}-purin-9-yl)-2,3-dihydroxy-cyclopentyl]-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a suspension of {(1S,2R,3S,4R)-4-[2-(2-amino-ethylcarbamoyl)-6-(2,2-diphenyl-ethylamino)-purin-9-yl]-2,3-dihydroxy-cyclopentyl}-carbamic acid tert-butyl ester (2.5 g, 4.05 mmol) in IPA (10 ml) is added imidazole-1-carboxylic acid (3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-4-yl)-amide (Intermediate C) (151 ml of a 10 mg/ml solution in DCM, 5.56 mmol) and the reaction mixture is stirred at room temperature overnight. The solvent is removed in vacuo and the crude product is purified by chromatography on silica eluting with DCM/MeOH (25:1 increasing to 15:1). The resulting solid is further purified by dissolving in DCM and washing the solution with water, drying (MgSO4) and concentrating in vacuo to afford the title product. (MH+ 820.7)

Workup

  1. customThe solvent is removed in vacuo
  2. customthe crude product is purified by chromatography on silica eluting with DCM/MeOH (25:1 increasing to 15:1)
  3. customThe resulting solid is further purified
  4. dissolutionby dissolving in DCM
  5. washwashing the solution with water
  6. dry with materialdrying (MgSO4)
  7. concentrationconcentrating in vacuo

Sources & evidence

ORD record
ord-22b1ddd36a3344ee950151eede9430a2
Source dataset
uspto-grants-2012_09
Patent number
US08258141B2

Reaction notes

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