Bromide ion → HCID 86695485, compound

HRID 1487533Notes

Reaction equation

HRID 1487533 reaction equation
[NH2:1][C@H:2]([CH2:23][F:24])[C@@H:3]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:12]=[CH:13][C:14]([CH2:17][NH:18][S:19]([CH3:22])(=[O:21])=[O:20])=[N:15][CH:16]=2)=[CH:7][CH:6]=1)[OH:4].Br[CH2:26][C:27](Br)=[O:28].[Br-].[N-:31]=[N+:32]=[N-:33].[Na+]>C(OC(=O)C)C.CN(C)C=O.O>[N:31]([CH2:26][C:27]([NH:1][C@H:2]([CH2:23][F:24])[C@H:3]([OH:4])[C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[N:15][C:14]([CH2:17][NH:18][S:19]([CH3:22])(=[O:20])=[O:21])=[CH:13][CH:12]=2)=[CH:7][CH:6]=1)=[O:28])=[N+:32]=[N-:33]

Participants

8

Reactant 4

HCID 259Bromide ionHCID 33557Sodium AzideHCID 61147Bromoacetyl bromideHCID 86695483HCID 86695483, compound

Product 1

HCID 86695485HCID 86695485, compoundYield 30.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

To a slurry of N-((5-(4-((1R,2S)-2-amino-3-fluoro-1-hydroxypropyl) phenyl) pyridin-2-yl) methyl)methanesulfonamide (800 mg, 2.26 mmol) in ethylacetate/aqueous NaHCO3 (1:1) (10 mL) is slowly added bromoacetyl bromide (900 mg, 4.5 mmol) over a period of 20 minutes. Organic layer is separated and aqueous layer extracted with ethyl acetate (3×10 mL). Combined extract is dried over Na2SO4 and concentrated to get crude product. m/z (CI) M+H 474. A mixture of crude bromide (500 mg) and sodium azide (470 mg, 7.0 mmol) in dimethylformamide (6 mL) is heated for 30 min at 50° C. Reaction is cooled, diluted with water (10 mL) and extracted with ethyl acetate (3×15 mL). Combined extract is dried over Na2SO4, concentrated under vacuum and then obtained crude product purified on silica gel column using 0 to 5% methanol/CH2Cl2 to give the title compound (300 mg): 1H NMR (400 MHz, DMSO-d6) 2.95 (s, 3H), 3.71-3.87 (m, 2H), 4.22-4.42 (m, 4H), 4.47-4.58 (m, 0.5H), 4.50-4.70 (m, 0.5H), 4.83-4.93 (m, 1H), 5.83-5.93 (m, 1H), 7.47 (d, 2H), 7.54 (d, 1H), 7.64-7.77 (m, 3H), 8.06-8.20 (m, 2H), 8.83 (d, 1H). m/z (CI) M+H 437.

Workup

  1. customof 20 minutes
  2. customOrganic layer is separated
  3. extractionaqueous layer extracted with ethyl acetate (3×10 mL)
  4. extractionCombined extract
  5. dry with materialis dried over Na2SO4
  6. concentrationconcentrated
  7. customto get crude product
  8. customReaction
  9. temperatureis cooled
  10. extractionextracted with ethyl acetate (3×15 mL)
  11. extractionCombined extract
  12. dry with materialis dried over Na2SO4
  13. concentrationconcentrated under vacuum
  14. customobtained crude product
  15. custompurified on silica gel column

Sources & evidence

ORD record
ord-3160d8e021324d0284a2b143961a41c2
Source dataset
uspto-grants-2016_08
Patent number
US09428528B2

Reaction notes

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