Pyridine → 1-[3-(6-tert-butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-2-hydroxymethyl-phenyl]-6-(1,1-dioxo-1lambda*6*-thiomorpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile

HRID 1025641Notes

Reaction equation

HRID 1025641 reaction equation
[O:1]=[S:2]1(=[O:19])[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:20]([C:24]1[CH:25]=[C:26]2[C:31](=[C:32]([F:34])[CH:33]=1)[C:30](=[O:35])[N:29]([C:36]1[C:44]3[CH2:43][O:42]B(O)[C:40]=3[CH:39]=[CH:38][CH:37]=1)[N:28]=[CH:27]2)([CH3:23])([CH3:22])[CH3:21].N1C=CC=CC=1.[NH4+].[Cl-]>C([O-])(=O)C.[Cu+2].C([O-])(=O)C.ClCCCl>[C:20]([C:24]1[CH:25]=[C:26]2[C:31](=[C:32]([F:34])[CH:33]=1)[C:30](=[O:35])[N:29]([C:36]1[C:44]([CH2:43][OH:42])=[C:40]([N:14]3[C:12]4=[N:13][C:8]([N:5]5[CH2:4][CH2:3][S:2](=[O:1])(=[O:19])[CH2:7][CH2:6]5)=[CH:9][CH:10]=[C:11]4[C:16]([C:17]#[N:18])=[CH:15]3)[CH:39]=[CH:38][CH:37]=1)[N:28]=[CH:27]2)([CH3:23])([CH3:21])[CH3:22]

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 710366576-(1,1-dioxo-1lambda*6*-thiomorpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile

Product 1

HCID 710366551-[3-(6-tert-butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-2-hydroxymethyl-phenyl]-6-(1,1-dioxo-1lambda*6*-thiomorpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrileYield 8.3%

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalystHCID 111,2-DichloroethaneSolvent

Conditions

Temperature
45 °C

Procedure

In a 25 mL round-bottomed flask, 6-(1,1-dioxo-1lambda*6*-thiomorpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile (122 mg, 442 μmol), 6-tert-butyl-8-fluoro-2-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-4-yl)phthalazin-1(2H)-one (155 mg, 442 μmol, Eq: 1.00) and copper acetate (108 mg) were combined with 1,2-dichloroethane (3.89 ml) to give a blue suspension. Pyridine (69.8 mg, 71.4 μl, 883 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 HPLC to give 1-[3-(6-tert-butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-2-hydroxymethyl-phenyl]-6-(1,1-dioxo-1lambda*6*-thiomorpholin-4-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile (22 mg, 8%)

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-6bb0d3ba14ef428ea7578177cfecf735
Source dataset
uspto-grants-2014_05
Patent number
US08729078B2

Reaction notes

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