Acetic Acid → HCID 178448511, compound

HRID 1711398Notes

Reaction equation

HRID 1711398 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[CH2:28][CH2:27][NH: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:29](=O)[CH2:30][CH2:31][CH3:32].C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+]>ClCCCl.C(Cl)(Cl)Cl>[CH2:29]([N:26]1[CH2:27][CH2:28][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]1)[CH2:30][CH2:31][CH3:32]

Participants

8

Reactant 5

HCID 176Acetic Acid2×HCID 261ButanalHCID 14798Sodium HydroxideHCID 5049666Sodium triacetoxyborohydrideHCID 178527276HCID 178527276, compound

Product 1

HCID 178448511HCID 178448511, compoundYield 49.8%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolvent2×HCID 6212ChloroformSolvent

Procedure

A suspension of 3-(naphthalene-1-sulfonyl)-5-(pyrrolidin-3-yloxy)-1H-indazole (52.8 mg, 0.134 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 temperatures, under nitrogen, for 20 minutes, treated with additional acetic acid (0.2 mL, 3 mmol) and 1,2-dichloroethane, stirred at ambient temperature for 1 hour, 40 minutes, treated with sodium triacetoxyborohydride (96.7 mg, 0.457 mmol), stirred for 3 hours at ambient temperatures, diluted with chloroform and poured into excess 2.5 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 purified by flash chromatography using 0.25% ammonium hydroxide/2.5% methanol in chloroform to afford 5-(1-butyl-pyrrolidin-3-yloxy)-3-(naphthalene-1-sulfonyl)-1H-indazole as a light yellow foam, 30.0 mg (49.8% yield). The foam was dissolved in chloroform and methanol, treated with ethereal HCl and concentrated in vacuo at 83° C. for 13 hours to give the title product as a pale yellow foam, 26.9 mg, Mass spectrum (+EI, [M+H]+) m/z 450. 1HNMR (500 MHz, DMSO-d6): δ14.19 (s, 1H), 10.25-10.65 (m*, 1H), 8.75 (d, 1H, J=8.54 Hz), 8.56 (d, 1H, J=6.83 Hz), 8.28 (d, 1H, J=8.29 Hz), 8.03-8.05 (m, 1H), 7.71-7.75 (m, 1H), 7.56-7.65 (m, 3H), 7.27 (s, 1H), 7.12 (dd, 1H, J=9.15 Hz and 2.32 Hz), 5.19-5.24 (m, 1H), 3.39-3.96 (m*, 3H), 3.08-3.24 (m*, 3H), 2.00-2.63 (m*, 2H), 1.56-1.64 (m, 2H), 1.21-1.34 (m, 2H), 0.80-0.90 ppm (m, 3H). *Conformational isomers due to protonation of tertiary amine.

Workup

  1. stirringstirred at ambient temperature for 1 hour, 40 minutes
  2. stirringstirred for 3 hours at ambient temperatures
  3. customThe phases were separated
  4. washthe organic phase was washed with brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe resultant residue was purified by flash chromatography

Sources & evidence

ORD record
ord-b6fe608ea8dc43e38202298fc558edb0
Source dataset
uspto-grants-2010_09
Patent number
US07790751B2

Reaction notes

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