Boron tribromide → HCID 58777582, compound

HRID 1371727Notes

Reaction equation

HRID 1371727 reaction equation
[NH2:1][C:2]1[C:7]([C:8]([C:10]2[C:15]([O:16]C)=[C:14]([O:18]C)[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.B(Br)(Br)Br>C(Cl)Cl>[NH2:1][C:2]1[C:7]([C:8]([C:10]2[C:15]([OH:16])=[C:14]([OH:18])[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 25134Boron tribromideHCID 58777551HCID 58777551, compound

Product 1

HCID 58777582HCID 58777582, compoundYield 53.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of [4-amino-2-(1-methanesulfonyl-piperidin-4-ylamino)-pyrimidin-5-yl]-(2,3-difluoro-5,6-dimethoxy-phenyl)-methanone (100 mg, 0.212 mmol, Example 261) in methylene chloride (50 mL) cooled to −78° C. was added boron tribromide (2.19 mL, 2.190 mmol, 1 M solution in methylene chloride, Aldrich). The reaction mixture was warmed slowly to 0° C. over a period of 1 hour. After being stirred at 0° C. for 1 hour, the reaction was quenched with a solution of aqueous sodium bicarbonate. The aqueous layer was extracted with methylene chloride. The combined layers were washed with water and dried over anhydrous sodium sulfate. The solids were filtered off and the filtrate was concentrated in vacuo. Purification of the crude residue by reversed phase HPLC (C18, eluting with water and acetonitrile) yielded [4-amino-2-(1-methanesulfonyl-piperidin-4-ylamino)-pyrimidin-5-yl]-(2,3-difluoro-5,6-dihydroxy-phenyl)-methanone as yellow solids (50 mg, 52%). HR-MS (ES, m/z) calculated for C17H20N5O5SF2 [(M+H)+] 444.1151, observed 444.1148.

Workup

  1. customthe reaction was quenched with a solution of aqueous sodium bicarbonate
  2. extractionThe aqueous layer was extracted with methylene chloride
  3. washThe combined layers were washed with water
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationThe solids were filtered off
  6. concentrationthe filtrate was concentrated in vacuo
  7. customPurification of the crude residue
  8. washby reversed phase HPLC (C18, eluting with water and acetonitrile)

Sources & evidence

ORD record
ord-20fd62284a3d44c2a046f8c90853c1c9
Source dataset
uspto-grants-2007_01
Patent number
US07157455B2

Reaction notes

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