Hydrogen Bromide → (2R)-5-bromo-1,3-dihydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridin]-2'(1'H)-one

HRID 1038980Notes

Reaction equation

HRID 1038980 reaction equation
N[C:2]1[CH:3]=[C:4]2[C:17](=[CH:18][CH:19]=1)[CH2:16][C@:6]1([C:14]3[C:9](=[N:10][CH:11]=[CH:12][CH:13]=3)[NH:8][C:7]1=[O:15])[CH2:5]2.N([O-])=O.[Na+].[BrH:24]>O>[Br:24][C:2]1[CH:3]=[C:4]2[C:17](=[CH:18][CH:19]=1)[CH2:16][C@:6]1([C:14]3[C:9](=[N:10][CH:11]=[CH:12][CH:13]=3)[NH:8][C:7]1=[O:15])[CH2:5]2

Participants

5

Reactant 3

HCID 260Hydrogen BromideHCID 23668193Sodium NitriteHCID 53260812(R)-5-Amino-1,3-dihydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridin]-2'(1'H)-one2×

Product 1

HCID 58118675(2R)-5-bromo-1,3-dihydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridin]-2'(1'H)-one

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Conditions

Temperature
100 °C

Procedure

To a cooled 0° C. solution of (R)-5-Amino-1,3-dihydrospiro[indene-2,3′-pyrrolo[2,3-b]pyridin]-2′(1′H)-one (0.5 g, 2 mmol, Intermediate 1), in 48% HBr (4 mL) was added slowly over 10 minutes a solution of sodium nitrite (137 mg, 2 mmol) in water (0.6 mL with a 0.2 mL wash). After 5 minutes CuBr (285 mg, 2 mmole) was added and a condenser with nitrogen flow was attached. The reaction mixture was placed into a 100° C. bath and heated to 100° C. for 20 minutes. The reaction was diluted with water to obtain a large amount of precipitate. The reaction was quenched with concentrated aqueous NH4OH (about 2.5 mL) and the subsequently formed solid was collected by filtration and washed with water. The solid was air dried to obtain 740 mg of a free flowing solid, to which was added about 2 g of silica gel. The mixture was dry-loaded onto a silica gel column and the product was eluted using a tertiary solvent mixture/gradient (10-70%/80%-20%/10% EtOAc/Hex/DCM). The product containing fractions were combined and concentrated at reduced pressure to give the title compound. MS: m/z=315 (M+1).

Workup

  1. washwash)
  2. customa condenser with nitrogen flow was attached
  3. customwas placed into a 100° C.
  4. customto obtain a large amount of precipitate
  5. customThe reaction was quenched with concentrated aqueous NH4OH (about 2.5 mL)
  6. filtrationthe subsequently formed solid was collected by filtration
  7. washwashed with water
  8. customdried
  9. customto obtain 740 mg of
  10. additionto which was added about 2 g of silica gel
  11. washthe product was eluted
  12. additionThe product containing fractions
  13. concentrationconcentrated at reduced pressure

Sources & evidence

ORD record
ord-07f5254bc5b543549c4cf04f0bd9e6a4
Source dataset
uspto-grants-2013_10
Patent number
US08552023B2

Reaction notes

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