Aluminum(III) Chloride → [4-Amino-2-(1-methanesulfonyl-piperidin-4-ylamino)-pyrimidin-5-yl]-(2,3-difluoro-6-hydroxy-5-methoxy-phenyl)-methanone

HRID 1371726Notes

Reaction equation

HRID 1371726 reaction equation
[NH2:1][C:2]1[C:7]([C:8]([C:10]2[C:15]([O:16]C)=[C:14]([O:18][CH3:19])[CH:13]=[C:12]([F:20])[C:11]=2[F:21])=[O:9])=[CH:6][N:5]=[C:4]([NH:22][CH:23]2[CH2:28][CH2:27][N:26]([S:29]([CH3:32])(=[O:31])=[O:30])[CH2:25][CH2:24]2)[N:3]=1.[Cl-].[Al+3].[Cl-].[Cl-]>C(Cl)Cl>[NH2:1][C:2]1[C:7]([C:8]([C:10]2[C:15]([OH:16])=[C:14]([O:18][CH3:19])[CH:13]=[C:12]([F:20])[C:11]=2[F:21])=[O:9])=[CH:6][N:5]=[C:4]([NH:22][CH:23]2[CH2:24][CH2:25][N:26]([S:29]([CH3:32])(=[O:30])=[O:31])[CH2:27][CH2:28]2)[N:3]=1

Participants

4

Reactant 2

HCID 6451240Aluminum(III) ChlorideHCID 58777551HCID 58777551, compound

Product 1

HCID 58777669[4-Amino-2-(1-methanesulfonyl-piperidin-4-ylamino)-pyrimidin-5-yl]-(2,3-difluoro-6-hydroxy-5-methoxy-phenyl)-methanoneYield 52%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of [4-amino-2-(1-methanesulfonyl-piperidin-4-ylamino)-pyrimidin-5-yl]-(2,3-difluoro-5,6-dimethoxy-phenyl)-methanone (30 mg, 0.0636 mmol, Example 261) in methylene chloride (20 mL) cooled to 5° C. was added aluminum chloride (129 mg, 0.954 mmol, Fluka). The reaction mixture was stirred at room temperature for 24 hours and quenched with water. Tetrahydrofuran (40 mL) was added and the layers were separated. The organic layer was washed with water (1×5 mL), brine (1×5 mL) and dried over anhydrous sodium sulfate. The solids were filtered off and the filtrate was concentrated in vacuo. Purification of the crude residue by flash chromatography (Biotage system, 60 Å silica gel, eluting with ethyl acetate) yielded [4-amino-2-(1-methanesulfonyl-piperidin-4-ylamino)-pyrimidin-5-yl]-(2,3-difluoro-6-hydroxy-5-methoxy-phenyl)-methanone as yellow solids (15 mg, 52%). HR-MS (ES, m/z) calculated for C18H22N5O5SF2 [(M+H)+] 458.1307, observed 458.1304.

Workup

  1. customquenched with water
  2. additionTetrahydrofuran (40 mL) was added
  3. customthe layers were separated
  4. washThe organic layer was washed with water (1×5 mL), brine (1×5 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationThe solids were filtered off
  7. concentrationthe filtrate was concentrated in vacuo
  8. customPurification of the crude residue
  9. washby flash chromatography (Biotage system, 60 Å silica gel, eluting with ethyl acetate)

Sources & evidence

ORD record
ord-a4539a844fe644f28e56338990c965b7
Source dataset
uspto-grants-2007_01
Patent number
US07157455B2

Reaction notes

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