Water → HCID 68760394, compound

HRID 387564Notes

Reaction equation

HRID 387564 reaction equation
Br[C:2]1[C:3]([N:20]2[CH2:25][CH2:24][N:23]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:22][CH2:21]2)=[C:4]2[CH:10]=[N:9][N:8]([CH2:11][C:12]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=3)[C:5]2=[N:6][CH:7]=1.CCOCC.O.C[C:40]([N:42](C)C)=O>[C-]#N.[C-]#N.[Zn+2].[Zn].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[C:40]([C:2]1[C:3]([N:20]2[CH2:21][CH2:22][N:23]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:24][CH2:25]2)=[C:4]2[CH:10]=[N:9][N:8]([CH2:11][C:12]3[CH:13]=[CH:14][C:15]([O:18][CH3:19])=[CH:16][CH:17]=3)[C:5]2=[N:6][CH:7]=1)#[N:42]

Participants

9

Reactant 4

HCID 962WaterHCID 3283Diethyl EtherHCID 31374DimethylacetamideHCID 68760849tert-butyl 4-(5-bromo-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazine-1-carboxylate

Product 1

HCID 68760394HCID 68760394, compoundYield 89%

Reagents, catalysts & solvents 4

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 23994ZincCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Procedure

A solution of tert-butyl 4-(5-bromo-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazine-1-carboxylate (0.20 g, 0.398 mmol, see Example 1), Zn(CN)2 (0.0304 g, 0.259 mmol), Zn dust (0.00625 g, 0.0955 mmol), Pd2dba3 (0.00729 g, 0.00796 mmol) and 1,1′-bis(diphenylphosphino)ferrocene (“dppf”) (0.00883 g, 0.0159 mmol) in dimethylacetamide (“DMA”; 5 mL) were heated at 110° C. for 20 hours. Ether (50 mL) and H2O (20 mL) were then added. The organic layer was separated, washed with brine and dried over sodium sulfate. After removal of the solvent, the resulting residue was purified by column chromatography (hexane:ethyl acetate, 1:1) to give tert-butyl 4-(5-cyano-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazine-1-carboxylate (0.16 g, 89%) as a solid. MS APCI (+) m/z 449.1 detected. 1H NMR (400 Hz, DMSO-d6) δ 8.47 (s, 1H), 7.20 (d, J=8.8 Hz, 2H), 6.86 (d, J=8.8 Hz, 2H), 5.51 (s, 2H), 3.88 (m, 4H), 3.70 (s, 3H), 3.58 (m, 4H).

Workup

  1. customThe organic layer was separated
  2. washwashed with brine
  3. dry with materialdried over sodium sulfate
  4. customAfter removal of the solvent
  5. customthe resulting residue was purified by column chromatography (hexane:ethyl acetate, 1:1)

Sources & evidence

ORD record
ord-3be13f76dced4b4cb995021d80863ba2
Source dataset
uspto-grants-2013_02
Patent number
US08372842B2

Reaction notes

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