Ammonium Chloride → HCID 23156813, compound

HRID 1098292Notes

Reaction equation

HRID 1098292 reaction equation
Cl[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[C:19]([F:22])([F:21])[F:20])[NH:8][C:9]2=[O:12])=[CH:4][CH:3]=1.[NH:23]1[CH2:28][CH2:27][CH:26]([CH2:29][OH:30])[CH2:25][CH2:24]1.[Cl-].[NH4+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2N(C)C)CCCCC1>[OH:30][CH2:29][CH:26]1[CH2:27][CH2:28][N:23]([C:2]2[CH:11]=[C:10]3[C:5]([CH:6]=[C:7]([C:13]4[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=4[C:19]([F:22])([F:21])[F:20])[NH:8][C:9]3=[O:12])=[CH:4][CH:3]=2)[CH2:24][CH2:25]1

Participants

6

Reactant 3

HCID 25517Ammonium ChlorideHCID 4207714-PiperidinemethanolHCID 23156880HCID 23156880, compound

Product 1

HCID 23156813HCID 23156813, compoundYield 71.3%

Reagents, catalysts & solvents 2

HCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Procedure

8.65 ml (8.65 mmol) of a 1 M lithium bis(trimethylsilyl)amide THF solution was added to a mixture consisting of 400 mg (1.24 mmol) of the 7-chloro-3-(2-trifluoromethylphenyl)-2H-isoquinolin-1-one obtained in Step B of Example 1; 427.2 mg (3.708 mmol) of 4-piperidinemethanol; 29.2 mg (0.074 mmol) of 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl; and 28.3 mg (0.0309 mmol) of tris(dibenzylideneacetone)dipalladium. The obtained mixture was stirred under heating to reflux over a day and a night. Thereafter, the reaction solution was cooled to a room temperature, and a saturated ammonium chloride aqueous solution was then added thereto, followed by extraction with methylene chloride. Thereafter, the extract was washed with a saturated saline solution, and was then dried over anhydrous sodium sulfate. The extract was concentrated, and the obtained residue was then purified by silica gel column chromatography (methylene chloride:methanol=25:1 to 20:1), so as to obtain 355.6 mg (71%) of 7-(4-hydroxymethylpiperidin-1-yl)-3-(2-trifluoromethylphenyl)-2H-isoquinolin-1-one in the form of a brown solid.

Workup

  1. temperatureunder heating
  2. temperatureto reflux over a day and a night
  3. extractionfollowed by extraction with methylene chloride
  4. washThereafter, the extract was washed with a saturated saline solution
  5. dry with materialwas then dried over anhydrous sodium sulfate
  6. concentrationThe extract was concentrated
  7. customthe obtained residue was then purified by silica gel column chromatography (methylene chloride:methanol=25:1 to 20:1)

Sources & evidence

ORD record
ord-426b5bfc8ede4cc985454f965967fad6
Source dataset
uspto-grants-2012_03
Patent number
US08143274B2

Reaction notes

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