Formaldehyde → HCID 25001927, compound

HRID 1665819Notes

Reaction equation

HRID 1665819 reaction equation
Cl.Cl.[Cl:3][C:4]1[CH:12]=[C:11]2[C:7]([C:8]([C:19]([N:21]3[CH2:26][CH2:25][C:24]4([C:34]5[C:29](=[N:30][CH:31]=[CH:32][CH:33]=5)[CH2:28][O:27]4)[CH2:23][CH2:22]3)=[O:20])=[CH:9][N:10]2[CH2:13][C@@H:14]2[CH2:18][CH2:17][CH2:16][NH:15]2)=[CH:6][CH:5]=1.[CH2:35](N(CC)CC)C.C=O.C([BH3-])#N.[Na+]>CO>[Cl:3][C:4]1[CH:12]=[C:11]2[C:7]([C:8]([C:19]([N:21]3[CH2:26][CH2:25][C:24]4([C:34]5[C:29](=[N:30][CH:31]=[CH:32][CH:33]=5)[CH2:28][O:27]4)[CH2:23][CH2:22]3)=[O:20])=[CH:9][N:10]2[CH2:13][C@@H:14]2[CH2:18][CH2:17][CH2:16][N:15]2[CH3:35])=[CH:6][CH:5]=1

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 8471TriethylamineHCID 5003444Sodium cyanoborohydrideHCID 25001925HCID 25001925, compound

Product 1

HCID 25001927HCID 25001927, compoundYield 77%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 0.15 g (0.29 mmol) 1′-({6-chloro-1-[(2S)-pyrrolidin-2-ylmethyl]-1H-indol-3-yl}carbonyl)-7H-spiro[furo[3,4-b]pyridine-5,4′-piperidine]dihydrochloride, 0.10 ml (0.72 mmol) triethylamine and 0.070 g (2.3 mmol) paraformaldehyde in 3 ml methanol was heated at reflux for 2 h. Cooling the reaction mixture to 0° C. using an ice-water bath was followed by addition of 0.030 g (0.43 mmol) sodium cyanoborohydride. The reaction mixture was stirred at room temperature for 16 h, quenched with water and diluted with 1 M aqueous sodium hydroxide solution. The aqueous layer was extracted with three portions of ethyl acetate. The combined organic layers were dried over sodium sulfate and concentrated in vacuo. The crude product was purified by flash column chromatography (aminopropyl-modified silica gel) to give the title compound (0.10 g; 77%) as an off-white solid.

Workup

  1. temperatureat reflux for 2 h
  2. customquenched with water
  3. additiondiluted with 1 M aqueous sodium hydroxide solution
  4. extractionThe aqueous layer was extracted with three portions of ethyl acetate
  5. dry with materialThe combined organic layers were dried over sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by flash column chromatography (aminopropyl-modified silica gel)

Sources & evidence

ORD record
ord-59938880cb694cb19175d1bac39b3d23
Source dataset
uspto-grants-2011_10
Patent number
US08039624B2

Reaction notes

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