Diisopropylamine → HCID 71136229, compound

HRID 629914Notes

Reaction equation

HRID 629914 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.[CH:17](/B(O)O)=[CH:18]\[CH3:19].[CH:23](NC(C)C)(C)C>CN(C=O)C.O.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:23][C:12]([CH3:13])([CH3:14])[CH2:11][N:10]1[C:5]2[C:6](=[N:7][C:2](/[CH:17]=[CH:18]/[CH3:19])=[CH:3][CH:4]=2)[N:8]([CH3:16])[C:9]1=[O:15]

Participants

7

Reactant 3

HCID 7912DiisopropylamineHCID 6157276((1E)-prop-1-en-1-yl)boronic acidHCID 772308275-chloro-1-(cyclopropylmethyl)-3-methyl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one

Product 1

HCID 71136229HCID 71136229, compound

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

5-Chloro-1-(2,2-dimethylpropyl)-3-methyl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one (1-4, 1 g, 3.9 mmol, 1.0 equiv), (E)-prop-1-enylboronic acid (0.5 g, 5.9 mmol, 1.5 equiv), diisopropylamine (1.1 ml, 7.8 mmol, 2 equiv), triphenylphosphine-3,3′,3″-trisulfonic acid trisodium salt hydrate (0.27 g, 0.43 mmol, 0.11 equiv), and Pd(OAc)2 (44 mg, 0.197 mmol, 0.05 quiv) were dissolved in DMF (9.85 mL)/water (3.28 mL), placed in a sealed tube and heated to 100° C. for 18 h. Following this duration, LCMS showed complete consumption of 1-4. The contents were filtered through Celite and washed with ethyl acetate (10 mL). The filtrate was diluted with saturated NaHCO3 (50 mL) and the layers were separated. The aqueous layer was back-extracted with ethyl acetate (3×20 mL) and the combined organics were dried over Na2SO4, filtered and concentrated in vacuo to give a brown semi-solid. Purification by normal-phase HPLC (0-40% EtOAc:hexane) afforded 33-1 as a yellow solid. MS m/z (M+H): observed=260.1.

Workup

  1. customplaced in a sealed tube
  2. customconsumption of 1-4
  3. filtrationThe contents were filtered through Celite
  4. washwashed with ethyl acetate (10 mL)
  5. additionThe filtrate was diluted with saturated NaHCO3 (50 mL)
  6. customthe layers were separated
  7. extractionThe aqueous layer was back-extracted with ethyl acetate (3×20 mL)
  8. dry with materialthe combined organics were dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customto give a brown semi-solid
  12. customPurification by normal-phase HPLC (0-40% EtOAc:hexane)

Sources & evidence

ORD record
ord-c12735ba913b46a2ba8193f5e3771bf8
Source dataset
uspto-grants-2016_04
Patent number
US09315518B2

Reaction notes

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