4-(1-Piperidylmethyl)phenylboronic Acid → HCID 58266504, compound

HRID 1506034Notes

Reaction equation

HRID 1506034 reaction equation
C(OC(=O)[NH:7][C:8]1[N:16]=[CH:15][C:14]2[NH:13][C:12]3[N:17]=[CH:18][C:19](Br)=[CH:20][C:11]=3[C:10]=2[CH:9]=1)(C)(C)C.[N:23]1([CH2:29][C:30]2[CH:35]=[CH:34][C:33](B(O)O)=[CH:32][CH:31]=2)[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1>C(#N)C.C([O-])(=O)C.[K+].CO.C(Cl)Cl.O>[N:23]1([CH2:29][C:30]2[CH:35]=[CH:34][C:33]([C:19]3[CH:18]=[N:17][C:12]4[NH:13][C:14]5[CH:15]=[N:16][C:8]([NH2:7])=[CH:9][C:10]=5[C:11]=4[CH:20]=3)=[CH:32][CH:31]=2)[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1

Participants

8

Reactant 2

HCID 230053434-(1-Piperidylmethyl)phenylboronic AcidHCID 68346934tert-butyl-{3-Bromo-9H-dipyrido[2,3-b;4',3'-d]pyrrol-6-yl}-carbamate

Product 1

HCID 58266504HCID 58266504, compoundYield 40%

Reagents, catalysts & solvents 5

HCID 887MethanolSolventHCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent2×HCID 517044Potassium AcetateSolvent

Conditions

Temperature
140 °C

Procedure

A degassed mixture of tert-butyl-{3-Bromo-9H-dipyrido[2,3-b;4′,3′-d]pyrrol-6-yl}-carbamate (105 mg, 0.290 mmol), 4-piperidin-1-ylmethyl-phenyl boronic acid (73.7 mg, 0.336 mmol), and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (1:1) (17.8 mg, 2.18 μmol, 7.5 mol %) in acetonitrile (1.3 mL) and 1M aqueous potassium acetate (1.3 mL) was heated under microwave irradiation at 140° C. for 30 minutes. The cooled reaction mixture was diluted with 20% MeOH in DCM and water, and filtered to remove the solids. The filtrate layers were separated and the aqueous phase was extracted into 20% MeOH in DCM, and the combined organic phase concentrated in vacuo. The resultant residue was purified by preparative HPLC (0-30% MeCN in water (0.1% formic acid) over 30 min, 35 mL/min) to afford the title compound as a yellow solid (41 mg, 40%). 1H NMR (DMSO-D6, 400 MHz): 11.47 (s, 1H), 8.77 (d, J=2.0 Hz, 1H), 8.73 (d, J=2.0 Hz, 1H), 8.30 (s, 1H), 8.16 (s, 1H), 7.73 (d, J=8.1 Hz, 2H), 7.41 (d, J=8.1 Hz, 2H), 7.18 (s, 1H), 3.48 (s, 2H), 2.38 (m, 4H), 1.57-1.47 (m, 4H), 1.41 (m, 2H). LCMS (Method D): RT=6.20 min, M+H+=358.

Workup

  1. customThe cooled reaction mixture
  2. filtrationfiltered
  3. customto remove the solids
  4. customThe filtrate layers were separated
  5. extractionthe aqueous phase was extracted into 20% MeOH in DCM
  6. concentrationthe combined organic phase concentrated in vacuo
  7. customThe resultant residue was purified by preparative HPLC (0-30% MeCN in water (0.1% formic acid) over 30 min, 35 mL/min)

Sources & evidence

ORD record
ord-8765034b045e467d8936c38887ab1e88
Source dataset
uspto-grants-2015_12
Patent number
US09216980B2

Reaction notes

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