Triethylborane → 4,6-Diamino-2-ethyl-nicotinonitrile

HRID 1364533Notes

Reaction equation

HRID 1364533 reaction equation
[NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6](Br)[N:5]=[C:4]([NH:11]C(=O)C)[CH:3]=1.C([O-])([O-])=O.[Cs+].[Cs+].B(CC)(CC)[CH2:22][CH3:23]>CN(C=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([CH2:22][CH3:23])[N:5]=[C:4]([NH2:11])[CH:3]=1

Participants

6

Reactant 3

HCID 7357TriethylboraneHCID 10796Cesium carbonateHCID 11557905N-(4-Amino-6-bromo-5-cyano-pyridin-2-yl)-acetamide

Product 1

HCID 451224114,6-Diamino-2-ethyl-nicotinonitrileYield 40%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6228DimethylformamideSolvent

Procedure

A mixture of 4,6-diamino-2-bromo-nicotinonitrile from Example 65A (250 mg, 1.2 mmol), Pd(dppf)Cl2 (96 mg, 0.12 mmol), Cs2CO3 (576 mg, 1.8 mmol) in anhydrous DMF was flushed with nitrogen for 5 min before BEt3 (1.0 M solution in hexane, 1.42 mL, 1.4 mmol) was added. The sealed tube was heated@ 120° C. in a microwave reactor for 20 min. The reaction mixture was then partitioned between EtOAc and water, the organic layer was washed with water and brine, dried over Na2SO4, and concentrated in vacuo. The crude residue was purified by silica gel sep-pak, eluting with 30-50% EtOAc in hexane. The product was further purified by recrystalization from EtOAc/hexane to provide the titled compound as a light brown solid (77 mg, 40% yield). 1H NMR (300 MHz, DMSO-d6) δ 6.18 (s, 2H), 6.10 (s, 2H), 5.52 (s, 1H), 2.54 (q, J=7.6 Hz, 2H), 1.14 (t, J=7.6 Hz, 3H); MS (ESI) m/e 163 (M+H)+.

Workup

  1. additionwas added
  2. customThe reaction mixture was then partitioned between EtOAc and water
  3. washthe organic layer was washed with water and brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe crude residue was purified by silica gel sep-pak
  7. washeluting with 30-50% EtOAc in hexane
  8. customThe product was further purified by recrystalization from EtOAc/hexane

Sources & evidence

ORD record
ord-4fb4504028be4da0b68e5f907db26ce7
Source dataset
uspto-grants-2011_02
Patent number
US07888374B2

Reaction notes

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