Acetic Acid → HCID 178456296, compound

HRID 1711400Notes

Reaction equation

HRID 1711400 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.[CH3:29][C:30]([CH3:32])=O.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl.C(Cl)(Cl)Cl>[CH:30]([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)([CH3:32])[CH3:29]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 180AcetoneHCID 5049666Sodium triacetoxyborohydrideHCID 178527276HCID 178527276, compound

Product 1

HCID 178456296HCID 178456296, compoundYield 68.6%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6212ChloroformSolvent

Procedure

A suspension of 3-(naphthalene-1-sulfonyl)-5-(pyrrolidin-3-yloxy)-1H-indazole (59.8 mg, 0.152 mmol) in 1,2-dichloroethane was treated with acetone (0.1 mL, 1 mmol) and acetic acid (0.1 mL, 2 mmol), stirred for one hour at ambient temperatures, under nitrogen, treated with sodium triacetoxyborohydride (66.3 mg, 0.313 mmol), stirred for 4 hours, diluted with chloroform and washed sequentially with 1.0 N sodium hydroxide and brine, treated with methanol to aid in solubility, dried over anhydrous magnesium sulfate and concentrated in vacuo. The resultant residue was purified by flash chromatography using 0.2% ammonium hydroxide/2.0% methanol in chloroform to afford 5-(1-isopropyl-pyrrolidin-3-yloxy)-3-(naphthalene-1-sulfonyl)-1H-indazole as a very light yellow foam, 45.4 mg (68.6% yield). The foam was dispersed in methanol and chloroform, treated with isopropanolic HCL and concentrated in vacuo at 84° C. for 14 hours to give the title product as a light brown foam, 42.1 mg, Mass spectrum (+APPI, [M+H]+) m/z 436. 1HNMR (500 MHz, DMSO-d6): δ14.22 (d, 1H, J=4.76 Hz), 10.39-11.06 (m*, 1H), 8.75 (d, 1H, J=8.66 Hz), 8.55-8.59 (m, 1H), 8.27 (d, 1H, J=8.18 Hz), 8.04 (d, 1H, J=7.93 Hz), 7.71-7.75 (m, 1H), 7.56-7.64 (m, 3H), 7.25-7.28 (m, 1H), 7.09-7.15 (m, 1H), 5.19-5.22 (m, 1H), 3.39-3.87 (m*, 4H), 3.20-3.25 (m*, 1H), 2.02-2.53 (m, 2H), 1.24-1.28 ppm (m, 6H). *Conformational isomers due to protonation of tertiary amine.

Workup

  1. stirringstirred for 4 hours
  2. washwashed sequentially with 1.0 N sodium hydroxide and brine
  3. additiontreated with methanol
  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-ddfa55f7c02c4a29971eeacb1b444097
Source dataset
uspto-grants-2010_09
Patent number
US07790751B2

Reaction notes

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