Acetic Acid → HCID 178456298, compound

HRID 1711411Notes

Reaction equation

HRID 1711411 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.[CH3:30][C:31]([CH3:33])=O.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl.C(OCC)(=O)C>[CH:31]([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)([CH3:33])[CH3:30]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 180AcetoneHCID 5049666Sodium triacetoxyborohydrideHCID 178527277HCID 178527277, compound

Product 1

HCID 178456298HCID 178456298, compoundYield 52%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A suspension of 3-(1-naphthylsulfonyl)-5-(piperidin-4-yloxy)-1H-indazole (71.2 mg, 0.175 mmol) in 1,2-dichloroethane was treated sequentially with acetone (0.4 mL, 5 mmol) and acetic acid (0.13 mL, 2.3 mmol), stirred for 2 hours, treated portionwise with sodium triacetoxyborohydride (255 mg, 1.20 mmol), stirred for 25 hours at ambient temperatures under nitrogen, diluted with ethyl acetate and washed with 1.0 N sodium hydroxide and brine. The organic phase was treated with methanol and chloroform, dried over anhydrous magnesium sulfate and concentrated in vacuo. The resultant residue was purified by flash chromatography using 0.3-1.0% ammonium hydroxide/3.0-10% methanol in chloroform to afford 5-(1-isopropylpiperidin-4-yloxy)-3-(1-naphthylsulfonyl)-1H-indazole as a light orange foam, 40.9 mg (52.0% yield). The foam was dispersed in methanol and chloroform, treated with isopropanolic HCl and concentrated for 12 hours in vacuo to yield the title product as a light orange foam, 37 mg, Mass spectrum (−EI, [M−H]−) m/z 448. 1HNMR (300 MHz, DMSO-d6): δ14.11-14.15 (m*, 1H), 9.82-9.84 (m, 1H), 8.69-8.76 (m, 1H), 8.54-8.58 (m, 1H), 8.27 (d, 1H, J=8.30 Hz), 8.02-8.04 (m, 1H), 7.70-7.75 (m, 1H), 7.54-7.63 (m, 3H), 7.29-7.36 (m*, 1H), 7.07-7.21 (m* and dd*, 1H, J=9.15 Hz and 2.31 Hz), 4.60-4.81 (m*, 1H), 3.40-3.50 (m, 2H), 3.06-3.21 (m*, 3H), 2.10-2.20 (m, 2H), 2.00-2.08 (m, 1H), 1.80-1.95 (m, 1H), 1.22-1.28 ppm (m, 6H). *Conformational isomers due to protonation of tertiary amine.

Workup

  1. stirringstirred for 25 hours at ambient temperatures under nitrogen
  2. washwashed with 1.0 N sodium hydroxide and brine
  3. additionThe organic phase was treated with methanol and chloroform
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe resultant residue was purified by flash chromatography

Sources & evidence

ORD record
ord-2b9e03940c2d49cb84bf8845d986de03
Source dataset
uspto-grants-2010_09
Patent number
US07790751B2

Reaction notes

Loading…