Sodium Iodide → 9-({5-[6-Bromo-1-(phenylsulfonyl)-1H-indazol-4-yl]-1,3,4-oxadiazol-2-yl}methyl)-6-oxa-9-azaspiro[4.5]decane

HRID 38843Notes

Reaction equation

HRID 38843 reaction equation
[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][N:8]2[S:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)(=[O:13])=[O:12])=[C:4]([C:20]2[O:21][C:22]([CH2:25]Cl)=[N:23][N:24]=2)[CH:3]=1.[CH2:27]1[C:31]2([CH2:36][NH:35][CH2:34][CH2:33][O:32]2)[CH2:30][CH2:29][CH2:28]1.CCN(C(C)C)C(C)C.[I-].[Na+]>C(#N)C.C(Cl)Cl>[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][N:8]2[S:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)(=[O:13])=[O:12])=[C:4]([C:20]2[O:21][C:22]([CH2:25][N:35]3[CH2:36][C:31]4([CH2:27][CH2:28][CH2:29][CH2:30]4)[O:32][CH2:33][CH2:34]3)=[N:23][N:24]=2)[CH:3]=1

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 81531DiisopropylethylamineHCID 224171726-Oxa-9-azaspiro(4.5)decaneHCID 666956686-bromo-4-[5-(chloromethyl)-1,3,4-oxadiazol-2-yl]-1-(phenylsulfonyl)-1H-indazole

Product 1

HCID 666921539-({5-[6-Bromo-1-(phenylsulfonyl)-1H-indazol-4-yl]-1,3,4-oxadiazol-2-yl}methyl)-6-oxa-9-azaspiro[4.5]decaneYield 30%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
70 °C

Procedure

6-Bromo-4-[5-(chloromethyl)-1,3,4-oxadiazol-2-yl]-1-(phenylsulfonyl)-1H-indazole (200 mg, 0.441 mmol) in acetonitrile (2 ml) was treated with 6-oxa-9-azaspiro[4.5]decane (160 mg, 0.793 mmol), DIPEA (0.154 ml, 0.8825 mmol) and sodium iodide (66 mg, 0.44 mmol). The reaction mixture was heated at 70° C. for 5 h, then cooled, diluted with DCM and washed with aqueous HCl. The organic layer was separated using a hydrophobic frit, washed with water and the solvent removed under a stream of nitrogen. The resulting residue was purified by loading onto a silica cartridge (20 g) and eluting with 0-100% ethyl acetate/cyclohexane over 40 mins. The appropriate fractions were combined and evaporated to give the title compound as a yellow solid (74 mg).

Workup

  1. temperaturecooled
  2. washwashed with aqueous HCl
  3. customThe organic layer was separated
  4. washwashed with water
  5. customthe solvent removed under a stream of nitrogen
  6. customThe resulting residue was purified
  7. washeluting with 0-100% ethyl acetate/cyclohexane over 40 mins
  8. customevaporated

Sources & evidence

ORD record
ord-46150b26714e4701bbca5dd0130936c8
Source dataset
uspto-grants-2013_09
Patent number
US08524751B2

Reaction notes

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