Pyridine → 6-bromo-1-(3-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-2-(hydroxymethyl)phenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile

HRID 1025635Notes

Reaction equation

HRID 1025635 reaction equation
[Br:1][C:2]1[N:7]=[C:6]2[NH:8][CH:9]=[C:10]([C:11]#[N:12])[C:5]2=[CH:4][CH:3]=1.[C:13]([C:17]1[CH:18]=[C:19]2[C:24](=[C:25]([F:27])[CH:26]=1)[C:23](=[O:28])[N:22]([C:29]1[C:37]3[CH2:36][O:35]B(O)[C:33]=3[CH:32]=[CH:31][CH:30]=1)[N:21]=[CH:20]2)([CH3:16])([CH3:15])[CH3:14].N1C=CC=CC=1.[NH4+].[Cl-]>C([O-])(=O)C.[Cu+2].C([O-])(=O)C.ClCCCl>[Br:1][C:2]1[N:7]=[C:6]2[N:8]([C:33]3[CH:32]=[CH:31][CH:30]=[C:29]([N:22]4[N:21]=[CH:20][C:19]5[C:24](=[C:25]([F:27])[CH:26]=[C:17]([C:13]([CH3:14])([CH3:15])[CH3:16])[CH:18]=5)[C:23]4=[O:28])[C:37]=3[CH2:36][OH:35])[CH:9]=[C:10]([C:11]#[N:12])[C:5]2=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 1049PyridineHCID 25517Ammonium ChlorideHCID 710081996-tert-butyl-8-fluoro-2-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-4-yl)phthalazin-1(2H)-oneHCID 730128926-bromo-1H-pyrrolo(2,3-b)pyridine-3-carbonitrile

Product 1

HCID 866737236-bromo-1-(3-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-2-(hydroxymethyl)phenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrileYield 10.3%

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalystHCID 111,2-DichloroethaneSolvent

Conditions

Temperature
45 °C

Procedure

In a 25 mL round-bottomed flask, 6-bromo-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile (75.0 mg, 338 μmol, Eq: 1.19), 6-tert-butyl-8-fluoro-2-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-4-yl)phthalazin-1(2H)-one (100 mg, 284 μmol, Eq: 1.00) and copper acetate (52.2 mg) were combined with 1,2-dichloroethane (3.00 ml) to give a blue suspension. Pyridine (44.9 mg, 45.9 μl, 568 μmol, Eq: 2) was added. The reaction mixture was heated to 45° C. and stirred for 2 d. Mixture was poured into 20 mL sat NH4Cl and extracted with EtOAc (3×20 mL). The organic layers were dried over MgSO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 40 g, 25% to 45% EtOAc in hexanes) to give 6-bromo-1-(3-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-2-(hydroxymethyl)phenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile (16 mg, 10.3%).

Workup

  1. customto give a blue suspension
  2. additionMixture was poured into 20 mL
  3. extractionextracted with EtOAc (3×20 mL)
  4. dry with materialThe organic layers were dried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customThe crude material was purified by flash chromatography (silica gel, 40 g, 25% to 45% EtOAc in hexanes)

Sources & evidence

ORD record
ord-aed1e86a56174b99a363cda20257c97a
Source dataset
uspto-grants-2014_05
Patent number
US08729078B2

Reaction notes

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