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

HRID 1615813Notes

Reaction equation

HRID 1615813 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+].[NH4+].[OH-].[BrH:26]>O>[Br:26][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

6

Reactant 4

HCID 260Hydrogen BromideHCID 14923Ammonium HydroxideHCID 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 solution of (R)-5-amino-1,3-dihydrospiro[indene-2,3′-pyrrolo[2,3-b]pyridin]-2′(1′H)-one (500 mg, 1.99 mmol, described in Intermediate 3) in 48% HBr (4 mL) at 0° C. was added slowly over 10 min a solution of sodium nitrite (137 mg, 1.99 mmol) in water (0.8 mL). After 5 minutes CuBr (285 mg, 1.99 mmol) was added and the reaction mixture was placed into a 100° C. oil bath and heated at 100° C. for 20 min. The reaction mixture was then diluted with water followed by 2.5 mL of 30% NH4OH (2.5 mL) and the resulting solid was collected by filtration and washed with water. The solid was air dried and chromatographed by first mixing with silica and dry loading on a silica gel column. The product was eluted. with (10% MeOH/CH2Cl2). Concentration of the product containing fractions gave the title compound. to 740 mg and ˜2 g of silica gel was added. The mixture was dry-loaded on to a silica gel column and the product was eluted with a gradient of EtOAc:hexanes:CH2Cl2—10:80:10 to 70:20:10. The product containing fractions were combined and concentrated at reduced pressure to give the title compound. MS: m/z=315 (M+1).

Workup

  1. customwas placed into a 100° C.
  2. filtrationthe resulting solid was collected by filtration
  3. washwashed with water
  4. customdried
  5. customchromatographed
  6. additionby first mixing with silica
  7. customdry loading on a silica gel column
  8. washThe product was eluted
  9. additionConcentration of the product containing fractions

Sources & evidence

ORD record
ord-6432aff1c4324270a12aefd1e53b5f4c
Source dataset
uspto-grants-2014_07
Patent number
US08765759B2

Reaction notes

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