Dichloromethane → 6-(2-Aminopyrimidin-5-yl)-3-(4-piperidin-1-ylmethylphenyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrole

HRID 1888615Notes

Reaction equation

HRID 1888615 reaction equation
Cl[C:2]1[N:10]=[CH:9][C:8]2[NH:7][C:6]3[N:11]=[CH:12][C:13]([C:15]4[CH:20]=[CH:19][C:18]([CH2:21][N:22]5[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]5)=[CH:17][CH:16]=4)=[CH:14][C:5]=3[C:4]=2[CH:3]=1.[NH2:28][C:29]1[N:34]=[CH:33][C:32](B(O)O)=[CH:31][N:30]=1.ClCCl>C(#N)C.C(=O)([O-])[O-].[K+].[K+]>[NH2:28][C:29]1[N:34]=[CH:33][C:32]([C:2]2[N:10]=[CH:9][C:8]3[NH:7][C:6]4[N:11]=[CH:12][C:13]([C:15]5[CH:20]=[CH:19][C:18]([CH2:21][N:22]6[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]6)=[CH:17][CH:16]=5)=[CH:14][C:5]=4[C:4]=3[CH:3]=2)=[CH:31][N:30]=1

Participants

6

Reactant 3

HCID 6344DichloromethaneHCID 17750211(2-Aminopyrimidin-5-yl)boronic acidHCID 582667236-Chloro-3-(4-piperidin-1-ylmethyl-phenyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrole

Product 1

HCID 445464896-(2-Aminopyrimidin-5-yl)-3-(4-piperidin-1-ylmethylphenyl)-9H-dipyrido[2,3-b;4',3'-d]pyrroleYield 14%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolvent2×HCID 11430Potassium CarbonateSolvent2×

Conditions

Temperature
140 °C

Procedure

A degassed mixture of 6-chloro-3-(4-piperidin-1-ylmethylphenyl)-9H-dipyrido[2,3-b;4′,3′-d]pyrrole (74.4 mg, 0.197 mmol), 2-aminopyrimidine-5-boronic acid, pinacol ester (45.8 mg, 0.207 mmol), and [1,1′-bis(diphenylphosphino)ferrocene] dichloropalladium(II) complex with dichloromethane (1:1) (8.1 mg, 9.87 umol, 5.0 mol %) in acetonitrile (0.74 mL) and 1M aqueous potassium carbonate solution (0.74 mL) was heated under microwave irradiation (140° C.) for 30 minutes. Further portions of the boronate ester (1.0 eq) and catalyst (5 mol %), acetonitrile (0.74 mL), and 1M aqueous potassium carbonate solution (0.74 mL) were added and the mixture heated under microwave irradiation (140° C.) for an additional 30 minutes. The mixture was concentrated in vacuo and the residue dissolved in water and DMF, and acidified with 10% (v/v) sulfuric acid. The resultant solid was removed by filtration and the filtrate concentrated in vacuo. The resultant residue was dissolved in DMSO and purified by preparative HPLC [0-30% MeCN/water modified with 0.1% formic acid] to afford an orange fluffy solid (5.1 mg, 14%). LCMS (Method E): RT=5.45 min, M+H+=436.

Workup

  1. temperaturethe mixture heated under microwave irradiation (140° C.) for an additional 30 minutes
  2. concentrationThe mixture was concentrated in vacuo
  3. dissolutionthe residue dissolved in water
  4. customThe resultant solid was removed by filtration
  5. concentrationthe filtrate concentrated in vacuo
  6. dissolutionThe resultant residue was dissolved in DMSO
  7. custompurified by preparative HPLC [0-30% MeCN/water modified with 0.1% formic acid]

Sources & evidence

ORD record
ord-00077e5c3167471f8c0d63ec6011762a
Source dataset
uspto-grants-2013_08
Patent number
US08501765B2

Reaction notes

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