Sodium Iodide → HCID 86614402, compound

HRID 2223980Notes

Reaction equation

HRID 2223980 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]([C:17]([C:19]([NH:22][C:23]([CH2:25]/[CH:26]=[CH:27]/[C:28]2[CH:33]=[CH:32][C:31]([C:34]#[C:35][C:36]3[CH:44]=[CH:43][CH:42]=[C:41]4[C:37]=3[C:38]([O:45][C@@H:46]3[O:72][C@H:71]([CH2:73][O:74][C:75](=[O:80])[C:76]([CH3:79])([CH3:78])[CH3:77])[C@@H:63]([O:64][C:65](=[O:70])[C:66]([CH3:69])([CH3:68])[CH3:67])[C@H:55]([O:56][C:57](=[O:62])[C:58]([CH3:61])([CH3:60])[CH3:59])[C@H:47]3[O:48][C:49](=[O:54])[C:50]([CH3:53])([CH3:52])[CH3:51])=[N:39][NH:40]4)=[CH:30][CH:29]=2)=[O:24])([CH3:21])[CH3:20])=[O:18])[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[CH2:82][C:83]([NH2:85])=[O:84].C(=O)([O-])[O-].[Cs+].[Cs+].[I-].[Na+]>CC(C)=O.C(OCC)C>[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]([C:17]([C:19]([NH:22][C:23]([CH2:25]/[CH:26]=[CH:27]/[C:28]2[CH:29]=[CH:30][C:31]([C:34]#[C:35][C:36]3[CH:44]=[CH:43][CH:42]=[C:41]4[C:37]=3[C:38]([O:45][C@@H:46]3[O:72][C@H:71]([CH2:73][O:74][C:75](=[O:80])[C:76]([CH3:79])([CH3:78])[CH3:77])[C@@H:63]([O:64][C:65](=[O:70])[C:66]([CH3:69])([CH3:68])[CH3:67])[C@H:55]([O:56][C:57](=[O:62])[C:58]([CH3:59])([CH3:60])[CH3:61])[C@H:47]3[O:48][C:49](=[O:54])[C:50]([CH3:53])([CH3:52])[CH3:51])=[N:39][N:40]4[CH2:82][C:83](=[O:84])[NH2:85])=[CH:32][CH:33]=2)=[O:24])([CH3:20])[CH3:21])=[O:18])[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 10796Cesium carbonateHCID 696322-BromoacetamideHCID 86614401HCID 86614401, compound

Product 1

HCID 86614402HCID 86614402, compoundYield 70.3%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 3283Diethyl EtherSolvent

Procedure

To a solution of 4-[2-(4-{(E)-3-[1-{[4-(benzyloxy-carbonyl)piperazin-1-yl]carbonyl}-1-(methyl)ethyl-carbamoyl]prop-1-enyl}phenyl)ethynyl]-3-(2,3,4,6-tetra-O-pivaloyl-β-D-glucopyranosyloxy)-1H-indazole (73 mg) in acetone (4 mL) were added 2-bromoacetoamide (18 mg), cesium carbonate (54 mg) and a catalytic amount of sodium iodide, and the mixture was stirred at room temperature for5 hours. The reaction mixture was diluted with diethyl ether, and the resulting mixture was washed with water twice and brine, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent:dichloromethane/methanol=40/1-30/1) to give 4-[2-(4-{(E)-3-[1-{[4-(benzyloxycarbonyl)piperazin-1-yl]carbonyl}-l-(methyl)ethylcarbamoyl]prop-l-enyl}-phenyl)ethynyl]-1-carbamoylmethyl-3-(2,3,4,6-tetra-O-pivaloyl-β-D-glucopyranosyloxy)-1H-indazole (54 mg). The title compound (10 mg) was prepared in a similar manner to that described in Example 109 using this material as the starting material.

Workup

  1. washthe resulting mixture was washed with water twice
  2. dry with materialbrine, and dried over anhydrous magnesium sulfate
  3. customThe solvent was removed under reduced pressure
  4. customthe residue was purified by column chromatography on silica gel (eluent:dichloromethane/methanol=40/1-30/1)

Sources & evidence

ORD record
ord-a0b61b7113f943619623cf98db7e6563
Source dataset
uspto-grants-2008_05
Patent number
US07375113B2

Reaction notes

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