Toluene → 1-{4-[9-[(1R,2S,3R,4S)-2,3-Dihydroxy-4-(4-methyl-pyrazol-1-yl)-cyclopentyl]-6-(2,2-diphenyl-ethylamino)-9H-purin-2-ylamino]-cyclohexyl}-3-(3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-yl)-urea Trifluoroacetate

HRID 1641910Notes

Reaction equation

HRID 1641910 reaction equation
[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[NH2:8][CH:9]1[CH2:14][CH2:13][CH:12]([NH:15][C:16]2[N:24]=[C:23]3[C:19]([N:20]=[CH:21][N:22]3[C@@H:25]3[CH2:29][C@H:28]([N:30]4[CH:34]=[C:33]([CH3:35])[CH:32]=[N:31]4)[C@@H:27]([OH:36])[C@H:26]3[OH:37])=[C:18]([NH:38][CH2:39][CH:40]([C:47]3[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=3)[C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)[N:17]=2)[CH2:11][CH2:10]1.C1(C)C=CC=CC=1.CC(O)C.[N:64]1[CH:69]=[CH:68][CH:67]=[CH:66][C:65]=1[N:70]1[CH2:75][CH2:74][CH:73]([NH:76][C:77](N2C=CN=C2)=[O:78])[CH2:72][CH2:71]1>C(Cl)Cl>[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[OH:37][C@@H:26]1[C@H:27]([OH:36])[C@@H:28]([N:30]2[CH:34]=[C:33]([CH3:35])[CH:32]=[N:31]2)[CH2:29][C@H:25]1[N:22]1[CH:21]=[N:20][C:19]2[C:23]1=[N:24][C:16]([NH:15][CH:12]1[CH2:11][CH2:10][CH:9]([NH:8][C:77]([NH:76][CH:73]3[CH2:72][CH2:71][N:70]([C:65]4[CH:66]=[CH:67][CH:68]=[CH:69][N:64]=4)[CH2:75][CH2:74]3)=[O:78])[CH2:14][CH2:13]1)=[N:17][C:18]=2[NH:38][CH2:39][CH:40]([C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)[C:47]1[CH:48]=[CH:49][CH:50]=[CH:51][CH:52]=1

Participants

6

Reactant 4

HCID 1140TolueneHCID 3776IsopropanolHCID 21978278N-[1-(2-pyridinyl)-4-piperidinyl]-1H-imidazole-1-carboxamideHCID 66736662(1R,2S,3R,5S)-3-[2-(4-Amino-cyclohexylamino)-6-(2,2-diphenyl-ethylamino)-purin-9-yl]-5-(4-methyl-pyrazol-1-yl)-cyclopentane-1,2-diol trifluoroacetate

Product 1

HCID 866228111-{4-[9-[(1R,2S,3R,4S)-2,3-Dihydroxy-4-(4-methyl-pyrazol-1-yl)-cyclopentyl]-6-(2,2-diphenyl-ethylamino)-9H-purin-2-ylamino]-cyclohexyl}-3-(3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-yl)-urea Trifluoroacetate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

(1R,2S,3R,5S)-3-[2-(4-Amino-cyclohexylamino)-6-(2,2-diphenyl-ethylamino)-purin-9-yl]-5-(4-methyl-pyrazol-1-yl)-cyclopentane-1,2-diol trifluoroacetate (Example 1) (0.020 g, 0.028 mmol) is dissolved in DCM (2 ml). Toluene (2 ml) and iPrOH (1 ml) are added followed by N-[1-(2-pyridinyl)-4-piperidinyl]-1H-imidazole-1-carboxamide (which is prepared using the method described in international patent application WO 01/94368) (0.03 mmol of a 0.1 M solution in DCM). The dichloromethane is removed by vacuo and the reaction mixture is stirred at room temperature. The reaction is shown to be complete by LCMS after 48 hours. The solvent is removed in vacuo. The title compound is obtained by flash column chromatography (Isolute™ C18, 0-100% acetonitrile in water—0.1% TFA). MS (ES+) m/e 811.5 (MH+).

Workup

  1. customis prepared
  2. customThe dichloromethane is removed by vacuo
  3. customThe solvent is removed in vacuo

Sources & evidence

ORD record
ord-89af76e7d5ae4f7385c2196785b2b6e4
Source dataset
uspto-grants-2012_02
Patent number
US08114877B2

Reaction notes

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