Formaldehyde → 5-(1-methyl-pyrrolidin-3-yloxy)-3-(naphthalene-1-sulfonyl)-1H-indazole

HRID 1711401Notes

Reaction equation

HRID 1711401 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.C=O.[C:31](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CC#N>[CH3:31][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

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 178527276HCID 178527276, compound

Product 1

HCID 1784804955-(1-methyl-pyrrolidin-3-yloxy)-3-(naphthalene-1-sulfonyl)-1H-indazoleYield 37.9%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of 3-(naphthalene-1-sulfonyl)-5-(pyrrolidin-3-yloxy)-1H-indazole (73.4 mg, 0.187 mmol) in CH3CN was treated with 37% aqueous formaldehyde (0.15 mL, 2.0 mmol) and sodium triacetoxyborohydride (92.1 mg, 0.435 mmol), stirred for 3 hours at ambient temperatures and partitioned in chloroform and 1.0 N sodium hydroxide. The phases were separated; the organic phase was washed with 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 0.3% ammonium hydroxide/3.0% methanol in chloroform to give 5-(1-methyl-pyrrolidin-3-yloxy)-3-(naphthalene-1-sulfonyl)-1H-indazole as a light orange foam, 28.8 mg (37.9% yield). The foam was taken up in methanol and chloroform, treated with isopropanolic HCl and concentrated in vacuo at 84° C. for 14 hours to yield the title product as a light orange foam, 27.2 mg, Mass spectrum (+EI, [M+H]+) m/z 408. 1HNMR (500 MHz, DMSO-d6): δ14.20 (s, 1H), 10.38-10.60 (br, 1H), 8.74 (d, 1H, J=8.66 Hz), 8.54-8.56 (m, 1H), 8.28 (d, 1H, J=8.30 Hz), 8.03-8.05 (m, 1H), 7.71-7.75 (m, 1H), 7.56-7.65 (m, 3H), 7.28 (d, 1H, J=2.20 Hz), 7.12 (dd, 1H, J=9.15 Hz and 2.32 Hz), 5.22 (s, 1H), 3.31-3.74 (m*, 3H), 2.85 (s, 3H), 2.03-2.12 ppm (m, 1H). *Conformational isomers due to protonation of tertiary amine.

Workup

  1. custompartitioned in chloroform
  2. customThe phases were separated
  3. washthe organic phase was washed with brine
  4. additiontreated with methanol
  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-09480762fa5b4f8da7faa7ba0d00b93c
Source dataset
uspto-grants-2010_09
Patent number
US07790751B2

Reaction notes

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