4-(1-Piperidylmethyl)phenylboronic Acid → HCID 58266539, compound

HRID 1505972Notes

Reaction equation

HRID 1505972 reaction equation
[C:1]1([S:7]([N:10]2[C:14]3[CH:15]=[N:16][C:17]([C:20]#[N:21])=[C:18]([OH:19])[C:13]=3[C:12]3[CH:22]=[C:23](Br)[CH:24]=[N:25][C:11]2=3)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[N:27]1([CH2:33][C:34]2[CH:39]=[CH:38][C:37](B(O)O)=[CH:36][CH:35]=2)[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1>C([O-])(=O)C.[K+].C(#N)C.C(OCC)(=O)C.O.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]>[C:1]1([S:7]([N:10]2[C:14]3[CH:15]=[N:16][C:17]([C:20]#[N:21])=[C:18]([OH:19])[C:13]=3[C:12]3[CH:22]=[C:23]([C:37]4[CH:36]=[CH:35][C:34]([CH2:33][N:27]5[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]5)=[CH:39][CH:38]=4)[CH:24]=[N:25][C:11]2=3)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

8

Reactant 2

HCID 230053434-(1-Piperidylmethyl)phenylboronic AcidHCID 582664728-(Benzenesulfonyl)-12-bromo-3-hydroxy-5,8,10-triazatricyclo[7.4.0.02,7]trideca-1(9),2,4,6,10,12-hexaene-4-carbonitrile

Product 1

HCID 58266539HCID 58266539, compoundYield 32.7%

Reagents, catalysts & solvents 5

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolventHCID 517044Potassium AcetateSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of 9-benzenesulfonyl-3-bromo-5-hydroxy-9H-dipyrido[2,3-b;4′,3′-d]pyrrole-6-carbonitrile (150 mg, 0.35 mmol), 4-piperidin-1-ylmethylphenyl boronic acid (126 mg, 0.6 mmol) and [1,1′-bis(diphenylphosphino) ferrocene]dichloropalladium(II) (27 mg, 0.04 mmol) in 2N aqueous potassium acetate (1.1 mL) and acetonitrile (1.4 mL) was heated under microwave irradiation at 140° C., for 30 minutes. The reaction mixture was diluted with ethyl acetate (10 mL) and water (10 mL) resulting in the formation of a precipitate. The supernatant liquors were decanted and the precipitate was dissolved in 10% methanol in DCM. The decanted liquors were partitioned and the aqueous phase was washed with 10% methanol in DCM (2×10 mL). The combined organic phases were concentrated in vacuo and the resultant residue purified by column chromatography (silica, 2 g cartridge, Si-SPE, 0-20% MeOH in DCM) afforded the crude product which was triturated with acetonitrile (1 mL) and methanol (1 mL) to afford the title compound as a beige solid (60 mg, 31%). LCMS (Method B): RT=2.65 min, M+H+=524.

Workup

  1. customresulting in the formation of a precipitate
  2. customThe supernatant liquors were decanted
  3. dissolutionthe precipitate was dissolved in 10% methanol in DCM
  4. customThe decanted liquors were partitioned
  5. washthe aqueous phase was washed with 10% methanol in DCM (2×10 mL)
  6. concentrationThe combined organic phases were concentrated in vacuo
  7. customthe resultant residue purified by column chromatography (silica, 2 g cartridge, Si-SPE, 0-20% MeOH in DCM)
  8. customafforded the crude product which
  9. customwas triturated with acetonitrile (1 mL) and methanol (1 mL)

Sources & evidence

ORD record
ord-80b736020fdc4df7b5d8856221cb477e
Source dataset
uspto-grants-2015_12
Patent number
US09216980B2

Reaction notes

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