Acetic Acid → HCID 24962016, compound

HRID 244434Notes

Reaction equation

HRID 244434 reaction equation
[F:1][C:2]([F:35])([F:34])[C:3]([C:21]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[N:23]([CH2:30][CH2:31][CH:32]=O)[CH:22]=1)([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[N:10]([C:14]1[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=1)[N:9]=[CH:8]2)[OH:4].C(O)(=O)C.[NH:40]1[CH2:45][CH2:44][CH:43]([CH2:46][OH:47])[CH2:42][CH2:41]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClC(Cl)C.O>[F:34][C:2]([F:1])([F:35])[C:3]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[N:10]([C:14]1[CH:15]=[CH:16][C:17]([F:20])=[CH:18][CH:19]=1)[N:9]=[CH:8]2)([C:21]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[N:23]([CH2:30][CH2:31][CH2:32][N:40]2[CH2:45][CH2:44][CH:43]([CH2:46][OH:47])[CH2:42][CH2:41]2)[CH:22]=1)[OH:4]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 4207714-PiperidinemethanolHCID 5049666Sodium triacetoxyborohydrideHCID 59437279HCID 59437279, compound

Product 1

HCID 24962016HCID 24962016, compoundYield 34.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 63651,1-DichloroethaneSolvent

Procedure

To a chilled (0° C.) solution of 100 mg (0.21 mmol) of 3-(3-{2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]-1-hydroxyethyl}indol-1-yl)propionaldehyde (prepared according to methods described in Examples 34 and 35) in dichloroethane was added 160 mg (2.6 mmol) acetic acid and 300 mg (2.6 mmol) 4-piperidinemethanol. The solution was warmed to room temperature, stirred for 30 minutes, and 0.1 g (0.5 mmol) of sodium triacetoxyborohydride was added. The solution was stirred at room temperature overnight. The reaction was diluted with water and extracted with ethyl acetate, the aqueous layer was separated and the organic layers were combined and washed with saturated sodium bicarbonate, brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by prep-HPLC to afford 42 mg (34.8%) of the title compound. MS m/z 581.6 (MH+).

Workup

  1. stirringThe solution was stirred at room temperature overnight
  2. extractionextracted with ethyl acetate
  3. customthe aqueous layer was separated
  4. washwashed with saturated sodium bicarbonate, brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by prep-HPLC

Sources & evidence

ORD record
ord-759e23bf9510469e882e5331a0c9dee2
Source dataset
uspto-grants-2014_02
Patent number
US08658637B2

Reaction notes

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