Pyridine → 7-(3-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-2-(hydroxymethyl)phenyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile

HRID 1025617Notes

Reaction equation

HRID 1025617 reaction equation
[N:1]1[C:6]2[NH:7][CH:8]=[C:9]([C:10]#[N:11])[C:5]=2[CH:4]=[N:3][CH:2]=1.[C:12]([C:16]1[CH:17]=[C:18]2[C:23](=[C:24]([F:26])[CH:25]=1)[C:22](=[O:27])[N:21]([C:28]1[C:36]3[CH2:35][O:34]B(O)[C:32]=3[CH:31]=[CH:30][CH:29]=1)[N:20]=[CH:19]2)([CH3:15])([CH3:14])[CH3:13].N1C=CC=CC=1.ClC(Cl)C>C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[C:12]([C:16]1[CH:17]=[C:18]2[C:23](=[C:24]([F:26])[CH:25]=1)[C:22](=[O:27])[N:21]([C:28]1[C:36]([CH2:35][OH:34])=[C:32]([N:7]3[C:6]4[N:1]=[CH:2][N:3]=[CH:4][C:5]=4[C:9]([C:10]#[N:11])=[CH:8]3)[CH:31]=[CH:30][CH:29]=1)[N:20]=[CH:19]2)([CH3:15])([CH3:13])[CH3:14]

Participants

6

Reactant 4

HCID 1049PyridineHCID 63651,1-DichloroethaneHCID 226052697H-Pyrrolo[2,3-d]pyrimidine-5-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 710084077-(3-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-2-(hydroxymethyl)phenyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrileYield 31.6%

Reagents, catalysts & solvents 1

HCID 8895Cupric acetateCatalyst

Conditions

Temperature
80 °C

Procedure

In a 25 mL round-bottomed flask, 7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile (40.9 mg, 284 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 (100 mg, 284 μmol, Eq: 1.00), copper acetate (34.8 mg) and pyridine (44.9 mg, 45.9 μl, 568 μmol, Eq: 2) were combined with dichloroethane to give a dark blue suspension. The reaction mixture was flushed with nitrogen. The reaction mixture was heated to 80° C. and stirred for 16 hr. The reaction was diluted with sat NH4Cl (50 mL) and extracted with EtOAc (3×50 mL). The mixture was separated by flash column using 30-50% EtOAc in hexanes to give the 7-[3-(6-tert-Butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-2-hydroxymethyl-phenyl]-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile (42 mg, 31%) as a lyophilized white powder.

Workup

  1. customto give a dark blue suspension
  2. customThe reaction mixture was flushed with nitrogen
  3. additionThe reaction was diluted with sat NH4Cl (50 mL)
  4. extractionextracted with EtOAc (3×50 mL)
  5. customThe mixture was separated by flash column

Sources & evidence

ORD record
ord-cd960f89a2bf43c2b84893f4ef84114d
Source dataset
uspto-grants-2014_05
Patent number
US08729078B2

Reaction notes

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