1,2-Dichloroethane → 1-(3-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-2-(hydroxymethyl)phenyl)-6-(4-methylpiperazin-1-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile

HRID 1025622Notes

Reaction equation

HRID 1025622 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]2[N:13]=[C:12]3[NH:14][CH:15]=[C:16]([C:17]#[N:18])[C:11]3=[CH:10][CH:9]=2)[CH2:4][CH2:3]1.[C:19]([C:23]1[CH:24]=[C:25]2[C:30](=[C:31]([F:33])[CH:32]=1)[C:29](=[O:34])[N:28]([C:35]1[C:43]3[CH2:42][O:41]B(O)[C:39]=3[CH:38]=[CH:37][CH:36]=1)[N:27]=[CH:26]2)([CH3:22])([CH3:21])[CH3:20].ClCCCl.N1C=CC=CC=1>C([O-])(=O)C.[Cu+2].C([O-])(=O)C.CCOC(C)=O>[C:19]([C:23]1[CH:24]=[C:25]2[C:30](=[C:31]([F:33])[CH:32]=1)[C:29](=[O:34])[N:28]([C:35]1[C:43]([CH2:42][OH:41])=[C:39]([N:14]3[C:12]4=[N:13][C:8]([N:5]5[CH2:4][CH2:3][N:2]([CH3:1])[CH2:7][CH2:6]5)=[CH:9][CH:10]=[C:11]4[C:16]([C:17]#[N:18])=[CH:15]3)[CH:38]=[CH:37][CH:36]=1)[N:27]=[CH:26]2)([CH3:22])([CH3:20])[CH3:21]

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 1049PyridineHCID 710081476-(4-methylpiperazin-1-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrileHCID 710081996-tert-butyl-8-fluoro-2-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-4-yl)phthalazin-1(2H)-one

Product 1

HCID 710080431-(3-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-2-(hydroxymethyl)phenyl)-6-(4-methylpiperazin-1-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrileYield 17%

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
45 °C

Procedure

In a 25 mL round-bottomed flask, 6-(4-methylpiperazin-1-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile (110 mg, 456 μmol), 6-tert-butyl-8-fluoro-2-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-4-yl)phthalazin-1(2H)-one (177 mg, 501 μmol, Eq: 1.10) and copper acetate (112 mg) were combined with 1,2-dichloroethane (3.03 ml) to give a blue suspension. Pyridine (72.1 mg, 73.7 μl, 912 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 EtOAc and extracted with sat NH4Cl (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) to give 1-(3-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-2-(hydroxymethyl)phenyl)-6-(4-methylpiperazin-1-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile (43 mg, 17%) of off white solid.

Workup

  1. customto give a blue suspension
  2. extractionextracted with sat NH4Cl (3×20 mL)
  3. dry with materialThe organic layers were dried over MgSO4
  4. concentrationconcentrated in vacuo
  5. customThe crude material was purified by flash chromatography (silica gel, 40 g, 5% to 10% MeOH in DCM)

Sources & evidence

ORD record
ord-e4ab1b67ccb048cabcc2b00a73b68bbb
Source dataset
uspto-grants-2014_05
Patent number
US08729078B2

Reaction notes

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