Water → tert-butyl 1-(3-methyl-6-(5-(pyridin-3-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)pyridin-2-yl)piperidin-4-ylcarbamate

HRID 1775055Notes

Reaction equation

Cl[C:2]1[C:3]([N:31]2[CH2:36][CH2:35][CH:34]([NH:37][C:38](=[O:44])[O:39][C:40]([CH3:43])([CH3:42])[CH3:41])[CH2:33][CH2:32]2)=[N:4][C:5]([C:8]2[C:16]3[C:11](=[CH:12][N:13]=[C:14]([C:17]4[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=4)[CH:15]=3)[N:10]([CH2:23][O:24][CH2:25][CH2:26][Si:27]([CH3:30])([CH3:29])[CH3:28])[N:9]=2)=[CH:6][CH:7]=1.[CH3:45]B(O)O.C([O-])(=O)C.[K+].O>C(=O)([O-])[O-].[Na+].[Na+].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(#N)C>[CH3:45][C:2]1[C:3]([N:31]2[CH2:32][CH2:33][CH:34]([NH:37][C:38](=[O:44])[O:39][C:40]([CH3:43])([CH3:42])[CH3:41])[CH2:35][CH2:36]2)=[N:4][C:5]([C:8]2[C:16]3[C:11](=[CH:12][N:13]=[C:14]([C:17]4[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=4)[CH:15]=3)[N:10]([CH2:23][O:24][CH2:25][CH2:26][Si:27]([CH3:29])([CH3:30])[CH3:28])[N:9]=2)=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 150 °C

Procedure

In a microwave reaction vial was charged with tert-butyl 1-(3-chloro-6-(5-(pyridin-3-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)pyridin-2-yl)piperidin-4-ylcarbamate from Example 241 (72.1 mg, 0.113 mmol), Methyl boronic acid (34.0 mg, 0.567 mmol), 1,1′-Bis(diphenylphosphino)ferrocenepalladium (II) chloride (9.25 mg, 0.0113 mmol), 1.00 M of Potassium acetate in Water (0.17 mL, 0.17 mmol), 1.00 M of Sodium carbonate in Water (0.17 mL, 0.17 mmol), and Acetonitrile (3 mL). The reaction mixture was heated under microwave at 150° C. for 3 minutes. Another 5 equivalents of Methyl boronic acid was added and continue heated under microwave at 150° C. for 3 minutes. The same procedure was repeated 2 more times. The mixture was concentrated to afford crude tert-butyl 1-(3-methyl-6-(5-(pyridin-3-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)pyridin-2-yl)piperidin-4-ylcarbamate, which was dissolved in 1,4-Dioxane (5 mL) and treated with 4.0 M of Hydrogen chloride in 1,4-Dioxane (5 mL) overnight at room temperature. The mixture was then concentrated, and the residue was purified by reverse phase HPLC to afford 243 as an off-white solid (14.0 mg, 32%). 1H NMR (400 MHz, DMSO) δ 9.24 (d, J=17.9 Hz, 2H), 9.07 (s, 1H), 8.61 (s, 1H), 8.43 (d, J=7.8 Hz, 1H), 8.38 (s, 1H), 7.76 (d, J=7.6 Hz, 1H), 7.65 (d, J=7.6 Hz, 1H), 7.56 (d, J=4.6 Hz, 1H), 3.73 (d, J=11.9 Hz, 2H), 3.13 (s, 1H), 3.01 (d, J=11.6 Hz, 2H), 2.32 (s, 3H), 2.02 (d, J=12.0 Hz, 2H), 1.68 (d, J=11.1 Hz, 2H). ESI MS m/z=386.2 (M+1)

Workup

customIn a microwave reaction
temperaturecontinue heated under microwave at 150° C. for 3 minutes
concentrationThe mixture was concentrated

Sources & evidence

ORD record: ord-11735250342c4a43a0bc61b76a99e7c3
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09260425B2

Reaction notes

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