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

HRID 1025628Notes

Reaction equation

HRID 1025628 reaction equation
[CH2:1]([O:3][C:4]1[N:9]=[CH:8][C:7]([C:10]2[N:15]=[C:14]3[NH:16][CH:17]=[C:18]([C:19]#[N:20])[C:13]3=[CH:12][CH:11]=2)=[CH:6][CH:5]=1)[CH3:2].[C:21]([C:25]1[CH:26]=[C:27]2[C:32](=[C:33]([F:35])[CH:34]=1)[C:31](=[O:36])[N:30]([C:37]1[C:45]3[CH2:44][O:43]B(O)[C:41]=3[CH:40]=[CH:39][CH:38]=1)[N:29]=[CH:28]2)([CH3:24])([CH3:23])[CH3:22].N1C=CC=CC=1.[NH4+].[Cl-]>C([O-])(=O)C.[Cu+2].C([O-])(=O)C.ClCCCl>[C:21]([C:25]1[CH:26]=[C:27]2[C:32](=[C:33]([F:35])[CH:34]=1)[C:31](=[O:36])[N:30]([C:37]1[C:45]([CH2:44][OH:43])=[C:41]([N:16]3[C:14]4=[N:15][C:10]([C:7]5[CH:8]=[N:9][C:4]([O:3][CH2:1][CH3:2])=[CH:5][CH:6]=5)=[CH:11][CH:12]=[C:13]4[C:18]([C:19]#[N:20])=[CH:17]3)[CH:40]=[CH:39][CH:38]=1)[N:29]=[CH:28]2)([CH3:24])([CH3:22])[CH3:23]

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 710085446-(6-ethoxypyridin-3-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile

Product 1

HCID 710085481-(3-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-2-(hydroxymethyl)phenyl)-6-(6-ethoxypyridin-3-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrileYield 15%

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalystHCID 111,2-DichloroethaneSolvent

Conditions

Temperature
45 °C

Procedure

In a 25 mL round-bottomed flask, 6-(6-ethoxypyridin-3-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile (110 mg, 416 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 (161 mg, 458 μmol, Eq: 1.10) and copper acetate (102 mg) were combined with 1,2-Dichloroethane (3 ml) to give a blue suspension. Pyridine (65.8 mg, 67.3 μl, 832 μmol, 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 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 SFC to give 1-(3-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-2-(hydroxymethyl)phenyl)-6-(6-ethoxypyridin-3-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile (36 mg, 15%).

Workup

  1. customto give a blue suspension
  2. additionThe reaction mixture 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, 5% to 10% MeOH in DCM)

Sources & evidence

ORD record
ord-e753dd03e4a84991b4ccb0a1070d3d8e
Source dataset
uspto-grants-2014_05
Patent number
US08729078B2

Reaction notes

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