Formaldehyde → HCID 178480496, compound

HRID 1711410Notes

Reaction equation

HRID 1711410 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](O[BH-](OC(=O)C)OC(=O)C)(=O)C.C=O.O.[OH-].[Na+]>C(#N)C.C(Cl)(Cl)Cl>[CH3:30][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

Participants

8

Reactant 5

HCID 712FormaldehydeHCID 962WaterHCID 14798Sodium HydroxideHCID 2724942TriacetoxyborohydrideHCID 178527277HCID 178527277, compound

Product 1

HCID 178480496HCID 178480496, compoundYield 101.4%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6342AcetonitrileSolvent

Procedure

A suspension of 3-(1-naphthylsulfonyl)-5-(piperidin-4-yloxy)-1H-indazole (57.7 mg, 0.142 mmol) in acetonitrile was treated in three portions with odium triacetoxyborohydride (54 mg, 0.26 mmol) and 37% formaldehyde in water (0.1 mL, 1.3 mmol), stirred at ambient temperatures for 2.5 hours and poured into excess chloroform and 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. The resultant residue was purified by flash chromatography with 0.5% ammonium hydroxide/5.0% methanol in chloroform to give 5-(1-methylpiperidin-4-yloxy)-3-(1-naphthylsulfonyl)-1H-indazole (47.9 mg, 0.144 mmol) as a light orange foam. The foam was dispersed in methanol and chloroform, treated with isopropanolic HCl and concentrated in vacuo at 82° C. in for 10 hours to yield the title product as a light orange solid, mp 252-4° C.; Mass spectrum (+EI, [M+H]+) m/z 422. 1HNMR (300 MHz, DMSO-d6): δ14.16 (s, 1H), 10.06-10.17 (m*, 1H), 8.73-8.75 (m, 1H), 8.54-8.56 (m, 1H), 8.26-8.28 (m, 1H), 8.02-8.05 (m, 1H), 7.72 (t, 1H, J=7.81 Hz), 7.55-7.63 (m, 3H), 7.29-7.37 (m*, 1H), 7.10-7.20 (m*, 1H), 4.58-4.77 (m*, 1H), 3.45-3.50 (m, 1H), 3.07-3.20 (m, 2H), 2.75 (s, 3H), 1.70-2.20 ppm (m*, 4H). *Conformational isomers due to protonation of tertiary amine.

Workup

  1. customThe phases were separated
  2. washThe organic phase was washed with brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe resultant residue was purified by flash chromatography with 0.5% ammonium hydroxide/5.0% methanol in chloroform

Sources & evidence

ORD record
ord-6646ca23ecdf4ff285dc77bd2cd2348e
Source dataset
uspto-grants-2010_09
Patent number
US07790751B2

Reaction notes

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