Citric Acid → HCID 67198965, compound

HRID 510006Notes

Reaction equation

HRID 510006 reaction equation
[C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([Br:19])[CH:18]=[C:13]3[C:12](I)=[CH:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([Mg]Cl)(C)C.[C:26]([O:30][C:31](=[O:51])[N:32]([C:42]1[CH:47]=[CH:46][C:45]([CH:48]=[O:49])=[C:44]([F:50])[N:43]=1)[CH2:33][C:34]1[CH:39]=[CH:38][C:37]([O:40][CH3:41])=[CH:36][CH:35]=1)([CH3:29])([CH3:28])[CH3:27].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>O1CCCC1>[C:26]([O:30][C:31](=[O:51])[N:32]([C:42]1[CH:47]=[CH:46][C:45]([CH:48]([C:12]2[C:13]3[C:14](=[N:15][CH:16]=[C:17]([Br:19])[CH:18]=3)[N:10]([S:7]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)(=[O:9])=[O:8])[CH:11]=2)[OH:49])=[C:44]([F:50])[N:43]=1)[CH2:33][C:34]1[CH:35]=[CH:36][C:37]([O:40][CH3:41])=[CH:38][CH:39]=1)([CH3:29])([CH3:27])[CH3:28]

Participants

6

Reactant 4

HCID 311Citric AcidHCID 242292401-Benzenesulfonyl-5-bromo-3-iodo-1H-pyrrolo[2,3-b]pyridineHCID 57963046HCID 57963046, compoundHCID 178418918HCID 178418918, compound

Product 1

HCID 67198965HCID 67198965, compoundYield 88.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
5 °C

Procedure

To a solution of 1-benzenesulfonyl-5-bromo-3-iodo-1H-pyrrolo[2,3-b]pyridine (165, 1.00 g, 2.16 mmol) in 7 mL of tetrahydrofuran at −50° C. under nitrogen, isopropylmagnesium chloride (1.18 mL, 2.35 mmol) was added slowly. The reaction was warmed to 5° C. over 70 minutes, then cooled to −45° C. and (6-fluoro-5-formyl-pyridin-2-yl)-(4-methoxy-benzyl)-carbamic acid tert-butyl ester (83, 0.678 g, 1.88 mmol) in 3.0 mL of tetrahydrofuran was added. The reaction was allowed to warm to room temperature over 2-3 hours. The reaction was mixed with aqueous 1 N citric acid and extracted with ethyl acetate. The organic layer was washed with water and brine, then dried over magnesium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material was purified by silica gel column chromatography eluting with ethyl acetate and hexane. Appropriate fractions were combined and concentrated under vacuum to provide the desired compound as a white solid (166, 1.155 g). MS (ESI) [M+H]+=696.4 and 698.3.

Workup

  1. temperaturecooled to −45° C.
  2. temperatureto warm to room temperature over 2-3 hours
  3. extractionextracted with ethyl acetate
  4. washThe organic layer was washed with water and brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationthe filtrate concentrated under vacuum
  8. customThe resulting material was purified by silica gel column chromatography
  9. washeluting with ethyl acetate and hexane
  10. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-7e2b6349fac04344bb89fe3b7dcc31f9
Source dataset
uspto-grants-2015_08
Patent number
US09096593B2

Reaction notes

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