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

HRID 1025637Notes

Reaction equation

HRID 1025637 reaction equation
[CH:1]([C:3]1[N:8]=[C:7]2[NH:9][CH:10]=[C:11]([C:12]#[N:13])[C:6]2=[CH:5][CH:4]=1)=[CH2:2].[C:14]([C:18]1[CH:19]=[C:20]2[C:25](=[C:26]([F:28])[CH:27]=1)[C:24](=[O:29])[N:23]([C:30]1[C:38]3[CH2:37][O:36]B(O)[C:34]=3[CH:33]=[CH:32][CH:31]=1)[N:22]=[CH:21]2)([CH3:17])([CH3:16])[CH3:15].N1C=CC=CC=1.[NH4+].[Cl-]>C([O-])(=O)C.[Cu+2].C([O-])(=O)C.ClCCCl>[C:14]([C:18]1[CH:19]=[C:20]2[C:25](=[C:26]([F:28])[CH:27]=1)[C:24](=[O:29])[N:23]([C:30]1[C:38]([CH2:37][OH:36])=[C:34]([N:9]3[C:7]4=[N:8][C:3]([CH:1]=[CH2:2])=[CH:4][CH:5]=[C:6]4[C:11]([C:12]#[N:13])=[CH:10]3)[CH:33]=[CH:32][CH:31]=1)[N:22]=[CH:21]2)([CH3:17])([CH3:15])[CH3:16]

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 866737256-vinyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile

Product 1

HCID 866737241-(3-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-2-(hydroxymethyl)phenyl)-6-vinyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrileYield 13%

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalystHCID 111,2-DichloroethaneSolvent

Conditions

Temperature
45 °C

Procedure

In a 25 mL round-bottomed flask, 6-vinyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile (138 mg, 816 μmol, Eq: 1.00), 6-tert-butyl-8-fluoro-2-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-4-yl)phthalazin-1(2H)-one (287 mg, 816 μmol, Eq: 1.00) and copper acetate (200 mg) were combined with 1,2-Dichloroethane (3.58 ml) to give a blue suspension. Pyridine (129 mg, 132 μl, 1.63 mmol, Eq: 2) was added. The reaction mixture was heated to 45° C. and stirred for 2 d. The reaction mixture was poured into 20 mL sat NH4Cl and extracted with sat 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, 5% to 10% MeOH in DCM), then by HPLC to give 1-(3-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-2-(hydroxymethyl)phenyl)-6-vinyl-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile (51 mg, 13%).

Workup

  1. customto give a blue suspension
  2. additionThe reaction mixture was poured into 20 mL
  3. extractionextracted with sat 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, 5% to 10% MeOH in DCM)

Sources & evidence

ORD record
ord-0d88f75b517a4b99947fb0bcabfba9cf
Source dataset
uspto-grants-2014_05
Patent number
US08729078B2

Reaction notes

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