Acetic Acid → HCID 178527278, compound

HRID 1711413Notes

Reaction equation

HRID 1711413 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.[CH:29]1[CH:34]=[CH:33][C:32]([CH2:35][CH:36]=O)=[CH:31][CH:30]=1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+]>ClCCCl>[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][N:26]([CH2:36][CH2:35][C:32]5[CH:33]=[CH:34][CH:29]=[CH:30][CH:31]=5)[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

7

Reactant 5

HCID 176Acetic AcidHCID 998PhenylacetaldehydeHCID 14798Sodium HydroxideHCID 5049666Sodium triacetoxyborohydride2×HCID 178527276HCID 178527276, compound

Product 1

HCID 178527278HCID 178527278, compoundYield 36.5%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A suspension of 3-(1-naphthylsulfonyl)-5-(pyrrolidin-3-yloxy)-1H-indazole (51.8 mg, 0.132 mmol) in 1,2-dichloroethane was treated portionwise with phenacetaldehyde (0.2 mL, 0.2 mmol) and acetic acid (0.2 mL, 4 mmol), stirred for one hour at ambient temperature under nitrogen, treated with sodium triacetoxyborohydride (49.1 mg, 0.232 mmol), stirred for 2.5 hours, treated with sodium triacetoxyborohydride (37.5 mg, 0.177 mmol), stirred for 2.5 hours, poured into 1.0 N sodium hydroxide and extracted with chloroform. The extracts were combined, washed with brine, dried over anhydrous magnesium sulfate and concentrated in vacuo. The resultant residue was purified by flash chromatography using 100% chloroform and 0.05-0.2% ammonium hydroxide/0.5-2.0% methanol in chloroform to yield 3-(1-naphthylsulfonyl)-5-{[1-(2-phenylethyl)pyrrolidin-3-yl]oxy}-1H-indazole as a light yellow semi-solid, 24.6 mg (36.5% yield). The semi-solid was dissolved in methanol and chloroform, treated with isopropanolic HCl and concentrated in vacuo at 82° C. for 12 hours to give the title product as a brown foam, 24.6 mg, Mass spectrum (+ES, [M+H]+) m/z 498. 1HNMR (500 MHz, DMSO-d6): δ14.24 (d, 1H, J=4.88 Hz), 10.59-10.90 (m*, 1H), 8.77-8.79 (m, 1H), 8.59-8.60 (m, 1H), 8.31 (d, 1H, J=8.24 Hz), 8.07 (d, 1H, J=8.09 Hz), 7.75-7.78 (m, 1H), 7.60-7.68 (m, 3H), 7.24-7.37 (m, 6H), 7.15-7.19 (m, 1H), 5.25-5.31 (m*, 1H), 3.74-4.02 (m*, 2H), 3.31-3.55 (m*, 4H), 3.01-3.04 (m, 2H), 2.08-2.63 ppm (m*, 2H). *Conformational isomers due to protonation of tertiary amine.

Workup

  1. stirringstirred for 2.5 hours
  2. stirringstirred for 2.5 hours
  3. extractionextracted with chloroform
  4. washwashed with brine
  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-70c8fce1b09f42cb880cb3a0c67bd1be
Source dataset
uspto-grants-2010_09
Patent number
US07790751B2

Reaction notes

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