Sodium Iodide → 6-(4-(4-(2,3-dichlorophenyl)-1,4-diazepan-1-yl)butoxy)-1H-indazole

HRID 1750157Notes

Reaction equation

HRID 1750157 reaction equation
BrCCCOC1C=CC2SC=[N:11]C=2C=1.[Na+].[I-].[Cl:17][C:18]1[C:23]([Cl:24])=[CH:22][CH:21]=[CH:20][C:19]=1[N:25]1[CH2:31][CH2:30][CH2:29][N:28]([CH2:32][CH2:33][CH2:34][CH2:35][O:36][C:37]2[CH:46]=[C:45]3[C:40]([CH2:41]CC(=O)[NH:44]3)=[CH:39][CH:38]=2)[CH2:27][CH2:26]1.CCN(C(C)C)C(C)C>CC#N>[Cl:17][C:18]1[C:23]([Cl:24])=[CH:22][CH:21]=[CH:20][C:19]=1[N:25]1[CH2:31][CH2:30][CH2:29][N:28]([CH2:32][CH2:33][CH2:34][CH2:35][O:36][C:37]2[CH:46]=[C:45]3[C:40]([CH:41]=[N:11][NH:44]3)=[CH:39][CH:38]=2)[CH2:27][CH2:26]1

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 81531DiisopropylethylamineHCID 56597938Unc0006HCID 666315515-(3-Bromopropoxy)benzo[d]thiazole

Product 1

HCID 565982126-(4-(4-(2,3-dichlorophenyl)-1,4-diazepan-1-yl)butoxy)-1H-indazoleYield 59%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of intermediate 51 (54.2 mg, 0.20 mmol) and NaI (60.3 mg, 0.40 mmol) in CH3CN (3 mL) was heated to reflux for 30 min and then cooled to rt. To this mixture was added intermediate 2 (62.4 mg, 0.22 mmol), followed then by DIEA (0.077 mL, 0.44 mmol). The resulting mixture was heated to reflux and stirred for 4 h. Precipitated crystals were filtered off and the filtrate was evaporated under reduced pressure. The residue was extracted with EtOAc. The combined EtOAc layers were washed with brine, dried over anhydrous Na2SO4, concentrated in vacuo and purified by ISCO to give 6-(4-(4-(2,3-dichlorophenyl)-1,4-diazepan-1-yl)butoxy)-1H-indazole (compound 47) (50.8 mg, 59%). HPLC: 99%, RT 4.526 min. MS (ESI) m/z 433.20 [M+H]+.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 30 min
  3. temperatureThe resulting mixture was heated
  4. temperatureto reflux
  5. customPrecipitated crystals
  6. filtrationwere filtered off
  7. customthe filtrate was evaporated under reduced pressure
  8. extractionThe residue was extracted with EtOAc
  9. washThe combined EtOAc layers were washed with brine
  10. dry with materialdried over anhydrous Na2SO4
  11. concentrationconcentrated in vacuo
  12. custompurified by ISCO

Sources & evidence

ORD record
ord-0a33ef7f1c7d467f98a0de611fc1566e
Source dataset
uspto-grants-2015_10
Patent number
US09156822B2

Reaction notes

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