Acetic Acid → HCID 178527279, compound

HRID 1711412Notes

Reaction equation

HRID 1711412 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.[C:30]1([CH2:36][CH:37]=O)[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl.C(Cl)(Cl)Cl>[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][N:27]([CH2:37][CH2:36][C:30]5[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=5)[CH2:26][CH2:25]4)[CH:21]=3)[NH:16][N:15]=2)(=[O:12])=[O:13])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 998PhenylacetaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 178527277HCID 178527277, compound

Product 1

HCID 178527279HCID 178527279, compoundYield 67.8%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6212ChloroformSolvent

Procedure

A suspension of 3-(1-naphthylsulfonyl)-5-(piperidin-4-yloxy)-1H-indazole (53.9 mg, 0.132 mmol) in 1,2-dichloroethane was treated sequentially with phenylacetaldehyde (0.17 mL, 1.5 mmol) and acetic acid (1.7 mL, 3.0 mmol), stirred at ambient temperature for 1.5 hours, treated with sodium triacetoxyborohydride (66.9 mg, 0.316 mmol), stirred at ambient temperature for 3-19 hours, diluted with chloroform and washed with 1.0 N sodium hydroxide and brine. (Methanol was added to the organic phase to aid in solubility.) The organic phase was dried over anhydrous magnesium sulfate and concentrated in vacuo. The resultant residue was purified by flash chromatography using 0.1-0.5% ammonium hydroxide/1.0-5.0% methanol in chloroform to yield 3-(1-naphthylsulfonyl)-5-{[1-(2-phenylethyl)piperidin-4-yl]oxy}-1H-indazole as an orange foam (45.8 mg, 67.8%). The foam was dissolved in methanol and chloroform, treated with isopropanolic HCl and concentrated in vacuo for 13 hours at 86° C. to give the title product as an orange foam (43.4 mg); Mass spectrum (+EI, [M+H]+) m/z 512. 1HNMR (500 MHz, DMSO-d6): δ14.16 (d, 1H, J=4.52 Hz), 10.19-10.30 (m*, 1H), 8.70-8.76 (m, 1H), 8.56 (dd, 1H, J=7.32 Hz and 1.10 Hz), 8.27 (d, 1H, J=8.18 Hz), 8.04 (d, 1H, J=7.68 Hz), 7.70-7.75 (m, 1H), 7.55-7.63 (m, 3H), 7.10-7.39 (m*, 7H), 4.60-4.82 (m*, 1H), 3.60-3.65 (m, 1H), 3.38-3.45 (m, 1H), 3.30-3.36 (m*, 1H), 3.15-3.24 (m, 2H), 3.01-3.07 (m, 2H), 2.01-2.28 (m*, 3H), 1.80-1.95 ppm (m*, 1H). *Conformational isomers due to protonation of tertiary amine.

Workup

  1. stirringstirred at ambient temperature for 3-19 hours
  2. washwashed with 1.0 N sodium hydroxide and brine
  3. addition(Methanol was added to the organic phase
  4. dry with material) The organic phase was dried over anhydrous magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe resultant residue was purified by flash chromatography

Sources & evidence

ORD record
ord-61ccc32cd749468bb665202023c72151
Source dataset
uspto-grants-2010_09
Patent number
US07790751B2

Reaction notes

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