Tetrahydrofuran → 4-[1-(2,2-Dimethylpropyl)-3-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-5-yl]butanenitrile

HRID 629926Notes

Reaction equation

HRID 629926 reaction equation
Cl[C:2]1[N:7]=[C:6]2[N:8]([CH3:16])[C:9](=[O:15])[N:10]([CH2:11][CH:12]3[CH2:14][CH2:13]3)[C:5]2=[CH:4][CH:3]=1.[CH3:17]C(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.[Br-].[C:52]([CH2:54][CH2:55][CH2:56][Zn+])#[N:53].C1COCC1>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:17][C:12]([CH3:13])([CH3:14])[CH2:11][N:10]1[C:5]2[C:6](=[N:7][C:2]([CH2:56][CH2:55][CH2:54][C:52]#[N:53])=[CH:3][CH:4]=2)[N:8]([CH3:16])[C:9]1=[O:15]

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 772308275-chloro-1-(cyclopropylmethyl)-3-methyl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-oneHCID 178511034HCID 178511034, compound

Product 1

HCID 711367894-[1-(2,2-Dimethylpropyl)-3-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-5-yl]butanenitrile

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Procedure

To a stirred solution of 1-4 (0.40 g, 1.58 mmol), Pd(OAc)2 (0.02 g, 0.08 mmol), xphos (0.074 g, 0.16 mmol) in dioxane (12 mL) was added 3-cyanopropylzinc bromide 0.5M solution in THF (12.6 mL, 6.3 mmol) and the resulting mixture was microwave irradiated for 30 minutes at 100° C. The reaction was allowed to cool and partitioned between ethyl acetate and water. The organic phase was concentrated and flash column separation using a 0-60% ethyl acetate/hexane gradient gave 38-1. (0.42 g, 94%). LRMS (ES) (M+H)+: observed=287.2, calculated=287.4.

Workup

  1. customthe resulting mixture was microwave irradiated for 30 minutes at 100° C
  2. temperatureto cool
  3. custompartitioned between ethyl acetate and water
  4. concentrationThe organic phase was concentrated
  5. customflash column separation
  6. customgave 38-1

Sources & evidence

ORD record
ord-d48249a7ebab4037803046956120fdf4
Source dataset
uspto-grants-2016_04
Patent number
US09315518B2

Reaction notes

Loading…