Sodium Carbonate → 1-(cyclopropylmethyl)-6-(3,4,5-trimethoxyphenyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one

HRID 333165Notes

Reaction equation

HRID 333165 reaction equation
N1[C:9]2C(=C[C:6]([N:10]3[C:18]4[C:13](=[N:14][CH:15]=[C:16]([C:19]5[CH:24]=[C:23]([O:25][CH3:26])[C:22]([O:27][CH3:28])=[C:21]([O:29][CH3:30])[CH:20]=5)[CH:17]=4)[NH:12][C:11]3=[O:31])=[CH:7][CH:8]=2)C=C1.BrCC1CC1.C([O-])([O-])=O.[K+].[K+].C(O)(C(F)(F)F)=O.C(Cl)Cl.BrC1C=C2N(CC3CC3)C(=O)NC2=NC=1.COC1C=C(B(O)O)C=C(OC)C=1OC.C([O-])([O-])=O.[Na+].[Na+]>CC(C)=O.CC#N.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl>[CH:7]1([CH2:6][N:10]2[C:18]3[C:13](=[N:14][CH:15]=[C:16]([C:19]4[CH:24]=[C:23]([O:25][CH3:26])[C:22]([O:27][CH3:28])=[C:21]([O:29][CH3:30])[CH:20]=4)[CH:17]=3)[NH:12][C:11]2=[O:31])[CH2:9][CH2:8]1

Participants

11

Reactant 7

HCID 10340Sodium CarbonateHCID 11430Potassium CarbonateHCID 81503BromomethylcyclopropaneHCID 27343903,4,5-Trimethoxybenzeneboronic acidHCID 21863450Trifluoroacetic acid methylene chlorideHCID 667791621-(1H-indol-5-yl)-6-(3,4,5-trimethoxyphenyl)-1H-imidazo[4,5-b]pyridin-2(3H)-oneHCID 667792026-bromo-1-(cyclopropylmethyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one

Product 1

HCID 462357251-(cyclopropylmethyl)-6-(3,4,5-trimethoxyphenyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one

Reagents, catalysts & solvents 3

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 180AcetoneSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
150 °C

Procedure

Intermediate 5 from Example 124 was alkylated with (bromomethyl)cyclopropane using K2CO3 in acetone, after which it was deprotected using TFA/CH2Cl2. To the resulting 6-bromo-1-(cyclopropylmethyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one in CH3CN (1 mL) in a microwave reaction vial was added 3,4,5-trimethoxyphenylboronic acid (30 mg, 0.14 mmol), bis(triphenylphosphine)-palladium(II)dichloride (7.0 mg, 0.010 mmol), and 1 M Na2CO3 (1 mL). The resulting mixture was de-gassed with Ar for 10 min, after which it was heated at 150° C. for 10 min in a Personal Chemistry Optimizer. The resulting mixture was partitioned between EtOAc and 1 M NaOH. The organic layer was separated, dried over MgSO4, filtered, and stripped to give a residue that was purified via preparatory HPLC to give 3.7 mg of the title compound. HPLC retention time: 1.90 minutes; MS ESI (m/z): 356.2 (M+1)+, calc. 355.

Workup

  1. customThe resulting mixture was de-gassed with Ar for 10 min
  2. customThe resulting mixture was partitioned between EtOAc and 1 M NaOH
  3. customThe organic layer was separated
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customto give a residue that
  7. customwas purified via preparatory HPLC

Sources & evidence

ORD record
ord-a9c2dba0cf6b4440bd44d8aeeb56be64
Source dataset
uspto-grants-2014_11
Patent number
US08877772B2

Reaction notes

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