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

HRID 1025645Notes

Reaction equation

HRID 1025645 reaction equation
[CH3:1][N:2]([CH3:17])[CH2:3][CH2:4][NH:5][C:6]1[N:11]=[C:10]2[NH:12][CH:13]=[C:14]([C:15]#[N:16])[C:9]2=[CH:8][CH:7]=1.[C:18]([C:22]1[CH:23]=[C:24]2[C:29](=[C:30]([F:32])[CH:31]=1)[C:28](=[O:33])[N:27]([C:34]1[C:42]3[CH2:41][O:40]B(O)[C:38]=3[CH:37]=[CH:36][CH:35]=1)[N:26]=[CH:25]2)([CH3:21])([CH3:20])[CH3:19].N1C=CC=CC=1.[NH4+].[Cl-]>C([O-])(=O)C.[Cu+2].C([O-])(=O)C.ClCCCl>[C:18]([C:22]1[CH:23]=[C:24]2[C:29](=[C:30]([F:32])[CH:31]=1)[C:28](=[O:33])[N:27]([C:34]1[C:42]([CH2:41][OH:40])=[C:38]([N:12]3[C:10]4=[N:11][C:6]([NH:5][CH2:4][CH2:3][N:2]([CH3:17])[CH3:1])=[CH:7][CH:8]=[C:9]4[C:14]([C:15]#[N:16])=[CH:13]3)[CH:37]=[CH:36][CH:35]=1)[N:26]=[CH:25]2)([CH3:21])([CH3:19])[CH3:20]

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 710083456-(2-(dimethylamino)ethylamino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile

Product 1

HCID 710080741-(3-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-2-(hydroxymethyl)phenyl)-6-(2-(dimethylamino)ethylamino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrileYield 3.5%

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalystHCID 111,2-DichloroethaneSolvent

Conditions

Temperature
45 °C

Procedure

In a 25 mL round-bottomed flask, 6-(2-(dimethylamino)ethylamino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile (211 mg, 920 μmol), 6-tert-butyl-8-fluoro-2-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-4-yl)phthalazin-1(2H)-one (324 mg, 920 μmol, Eq: 1.00) and copper acetate (226 mg) were combined with 1,2-Dichloroethane (6.73 ml) to give a blue suspension. Pyridine (146 mg, 149 μl, 1.84 mmol, 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, 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-(2-(dimethylamino)ethylamino)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile (18 mg, 3.5%)

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, 5% to 10% MeOH in DCM)

Sources & evidence

ORD record
ord-2b28048b808740789ec46fa175dcfaa2
Source dataset
uspto-grants-2014_05
Patent number
US08729078B2

Reaction notes

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