Water → HCID 57646815, compound

HRID 1022859Notes

Reaction equation

HRID 1022859 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:16]=[C:17]3[C:22](=[CH:23][C:24]=2Br)[CH:21]=[N:20][CH:19]=[CH:18]3)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O.C(OCC)(=O)C.[CH3:33][N:34](C=O)C>[C-]#N.[C-]#N.[Zn+2].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:16]=[C:17]3[C:22](=[CH:23][C:24]=2[C:33]#[N:34])[CH:21]=[N:20][CH:19]=[CH:18]3)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 962WaterHCID 6228DimethylformamideHCID 8857Ethyl AcetateHCID 57646800HCID 57646800, compound

Product 1

HCID 57646815HCID 57646815, compound

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Procedure

Under argon atmosphere 35 mg (0.3 mmol) of Zn(CN)2 and 17 mg (0.05 eq) of Pd(PPh3)4 were added to a solution of 122 mg (0.3 mmol) of 4-(7-bromo-isoquinolin-6-yloxy)-piperidine-1-carboxylic acid tert-butyl ester (13) in DMF. The reaction was heated for 5 minutes to 150° C. in a microwave reactor (CEM Discovery). After cooling to room temperature water and ethyl acetate were added. The mixture was filtered through Celite, washed with ethyl acetate and concentrated. The crude product was purified by preparative HPLC to yield 77 mg of compound 16.

Workup

  1. temperatureThe reaction was heated for 5 minutes to 150° C. in a microwave reactor (CEM Discovery)
  2. additionwere added
  3. filtrationThe mixture was filtered through Celite
  4. washwashed with ethyl acetate
  5. concentrationconcentrated
  6. customThe crude product was purified by preparative HPLC

Sources & evidence

ORD record
ord-163ad860bbb744c789deb2463355d605
Source dataset
uspto-grants-2014_05
Patent number
US08722671B2

Reaction notes

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