Acetic Acid → HCID 178448512, compound

HRID 1711409Notes

Reaction equation

HRID 1711409 reaction equation
[C:1]1([S:11]([C:14]2[C:22]3[C:17](=[CH:18][CH:19]=[C:20]([O:23][CH:24]4[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]4)[CH:21]=3)[NH:16][N:15]=2)(=[O:13])=[O:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.[CH:30](=O)[CH2:31][CH2:32][CH3:33].C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+]>ClCCCl.C(Cl)(Cl)Cl>[CH2:30]([N:27]1[CH2:28][CH2:29][CH:24]([O:23][C:20]2[CH:21]=[C:22]3[C:17](=[CH:18][CH:19]=2)[NH:16][N:15]=[C:14]3[S:11]([C:1]2[C:10]3[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=3)[CH:4]=[CH:3][CH:2]=2)(=[O:12])=[O:13])[CH2:25][CH2:26]1)[CH2:31][CH2:32][CH3:33]

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 261ButanalHCID 14798Sodium HydroxideHCID 5049666Sodium triacetoxyborohydrideHCID 178527277HCID 178527277, compound

Product 1

HCID 178448512HCID 178448512, compoundYield 40%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6212ChloroformSolvent

Procedure

A suspension of 3-(1-naphthylsulfonyl)-5-(piperidin-4-yloxy)-1H-indazole (56.5 mg, 0.138 mmol) in 1,2-dichloroethane was treated sequentially with butyraldehyde (0.1 mL, 1 mmol) and acetic acid (0.1 mL, 2 mmol), stirred at ambient temperature for 3 hours, treated with sodium triacetoxyborohydride (46.5 mg, 0.220 mmol), stirred for 1 hour, 20 minutes under nitrogen at ambient temperatures, diluted with chloroform and poured into excess 1.0 N sodium hydroxide. The phases were separated. The organic phase was washed with brine, dried over anhydrous magnesium sulfate, and concentrated in vacuo. The resultant residue was twice purified by flash chromatography using 0.25-0.5% ammonium hydroxide/2.5-5.0% methanol in chloroform to afford 5-(1-butylpiperidin-4-yloxy)-3-(1-naphthylsulfonyl)-1H-indazole as a light orange foam, 25.6 mg (40.0% yield). The foam was dispersed in methanol, treated with ethereal HCl and concentrated in vacuo at 83° C. for 25 hours to give the title product as an orange foam, 22.0 mg, Mass spectrum (+EI, [M+H]+) m/z 464. 1HNMR (500 MHz, DMSO-d6): δ14.16 (d, 1H, J=4.15 Hz), 9.86-9.98 (m*, 1H), 8.73 (dd, 1H, J=15.74 Hz and 8.42 Hz), 8.54-8.56 (m, 1H), 8.27 (d, 1H, J=8.29 Hz), 8.02-8.05 (m, 1H), 7.70-7.75 (m, 1H), 7.54-7.63 (m, 3H), 7.28-7.38 (s* and s*, 1H), 7.09-7.20 (m*, 1H), 4.60-4.80 (m*, 1H), 3.52-3.55 (m, 1H), 3.32-3.35 (m, 1H), 3.00-3.16 (m, 4H), 2.06-2.16 (m, 2H), 1.97-2.00 (m, 1H), 1.79-1.88 (m, 1H), 1.60-1.67 (m, 2H), 1.25-1.34 (m, 2H), 0.92-0.87 ppm (m, 3H). *Conformational isomers due to protonation of tertiary amine.

Workup

  1. stirringstirred for 1 hour, 20 minutes under nitrogen at ambient temperatures
  2. customThe phases were separated
  3. washThe organic phase was washed with brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe resultant residue was twice purified by flash chromatography

Sources & evidence

ORD record
ord-5bbacdea0c724b8aafb9920f63c49b6f
Source dataset
uspto-grants-2010_09
Patent number
US07790751B2

Reaction notes

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