Acetic Acid → HCID 178456299, compound

HRID 1711408Notes

Reaction equation

HRID 1711408 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][CH3:32].C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+]>ClCCCl.C(OCC)(=O)C>[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]([CH2:30][CH2:31][CH3:32])[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

8

Reactant 5

HCID 176Acetic AcidHCID 527Propanal2×HCID 14798Sodium HydroxideHCID 5049666Sodium triacetoxyborohydrideHCID 178527277HCID 178527277, compound

Product 1

HCID 178456299HCID 178456299, compoundYield 81.8%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A suspension of 3-(1-naphthylsulfonyl)-5-(piperidin-4-yloxy)-1H-indazole (56.0 mg, 0.137 mmol) in 1,2-dichloroethane was treated sequentially with propionaldehyde (0.01 mL, 0.1 mmol) in 1,2-dichloroethane and acetic acid (0.1 mL, 2 mmol), stirred at ambient temperatures under nitrogen for 2 hours, treated with additional propionaldehyde (0.1 mL, 1 mmol) to aid in solubility, stirred at ambient temperatures for 1.5 hours, treated with sodium triacetoxyborohydride (59.8 mg, 0.283 mmol), stirred for 1.25 hours at ambient temperatures, diluted with ethyl acetate 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 at 81° C. for 20 minutes to yield 3-(1-naphthylsulfonyl)-5-(1-propylpiperidin-4-yloxy)-1H-indazole as a light orange solid, 50.4 mg (81.8% yield). The solid was dissolved in chloroform and methanol, treated with ethereal HCl and concentrated in vacuo at 82° C. for 15 hours to give the title product as a light orange semi-solid, 40.2 mg, Mass spectrum (+EI, [M+H]+) m/z 450. 1HNMR (500 MHz, DMSO-d6): δ14.16 (d, 1H, J=3.78 Hz), 9.97-10.10 (m*, 1H), 8.70-8.76 (m, 1H), 8.55 (dd, 1H, J=7.44 Hz and 1.22 Hz), 8.26-8.28 (m, 1H), 8.02-8.04 (m, 1H), 7.70-7.75 (m, 1H), 7.54-7.63 (m, 3H), 7.27-7.37 (s* and s*, 1H), 7.08-7.20 (dd* and m*, 1H, J=9.03 Hz and 2.08 Hz), 4.59-4.80 (m*, 1H), 3.50-3.53 (m, 1H), 3.31-3.34 (m, 1H), 2.97-3.19 (m, 4H), 2.08-2.15 (m, 2H), 1.96-2.00 (m, 1H), 1.80-1.90 (m, 1H), 1.63-1.72 (m, 2H), 0.86-0.91 ppm (m, 3H). *Conformational isomers due to protonation of tertiary amine.

Workup

  1. stirringstirred at ambient temperatures for 1.5 hours
  2. stirringstirred for 1.25 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 at 81° C. for 20 minutes

Sources & evidence

ORD record
ord-739be78f8611458dae5992da2ce1eeeb
Source dataset
uspto-grants-2010_09
Patent number
US07790751B2

Reaction notes

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