HCID 86676706, compound → HCID 71254059, compound

HRID 1775117Notes

Reaction equation

HRID 1775117 reaction equation
[CH2:1]=[C:2]([C:4]1[C:5]([N:33]2[CH2:38][CH2:37][CH2:36][C@H:35]([NH:39][C:40](=[O:46])[O:41][C:42]([CH3:45])([CH3:44])[CH3:43])[CH2:34]2)=[N:6][C:7]([C:10]2[C:18]3[C:13](=[CH:14][N:15]=[C:16]([C:19]4[CH:20]=[N:21][CH:22]=[CH:23][CH:24]=4)[CH:17]=3)[N:12]([CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:32])([CH3:31])[CH3:30])[N:11]=2)=[CH:8][CH:9]=1)[CH3:3].[H][H]>C(O)C.[OH-].[OH-].[Pd+2]>[CH:2]([C:4]1[C:5]([N:33]2[CH2:38][CH2:37][CH2:36][C@H:35]([NH:39][C:40](=[O:46])[O:41][C:42]([CH3:43])([CH3:45])[CH3:44])[CH2:34]2)=[N:6][C:7]([C:10]2[C:18]3[C:13](=[CH:14][N:15]=[C:16]([C:19]4[CH:20]=[N:21][CH:22]=[CH:23][CH:24]=4)[CH:17]=3)[N:12]([CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:32])([CH3:30])[CH3:31])[N:11]=2)=[CH:8][CH:9]=1)([CH3:3])[CH3:1]

Participants

5

Reactant 2

HCID 86676706HCID 86676706, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 71254059HCID 71254059, compound

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 702EthanolSolvent

Procedure

(S)-tert-butyl 1-(3-(prop-1-en-2-yl)-6-(5-(pyridin-3-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)pyridin-2-yl)piperidin-3-ylcarbamate (60.50 mg, 0.09426 mmol) and palladium hydroxide on carbon 20% (0.2:0.8, Palladium hydroxide:carbon black, 6.619 mg) in Ethanol (30 mL) in a round bottom flask was vacuumed and connected to a Hydrogen balloon. The mixture was stirred at room temperature over the weekend. The reaction mixture was filtered through Celite. The filtrate was concentrated to afford (S)-tert-butyl 1-(3-isopropyl-6-(5-(pyridin-3-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)pyridin-2-yl)piperidin-3-ylcarbamate, which was dissolved in Trifluoroacetic Acid (3 mL) and Methylene chloride (3 mL), and treated with Trifluoromethanesulfonic acid (83.4 uL, 0.943 mmol) and Triethylsilane (150.6 uL, 0.943). The resulting mixture was stirred at room temperature overnight. The mixture was then concentrated, and the residue was purified by reverse phase HPLC to afford 328 as an off-white solid (8.2 mg, 21%) over two steps. 1H NMR (400 MHz, DMSO) δ 9.31 (d, J=2.1 Hz, 1H), 9.22 (s, 1H), 9.06 (s, 1H), 8.61 (dd, J=4.7, 1.3 Hz, 1H), 8.45 (d, J=8.0 Hz, 1H), 8.32 (s, 1H), 7.88 (d, J=7.9 Hz, 1H), 7.82 (d, J=7.9 Hz, 1H), 7.54 (dd, J=8.0, 4.8 Hz, 1H), 2.90 (d, J=9.1 Hz, 2H), 2.00 (d, J=12.6 Hz, 1H), 1.90 (d, J=13.4 Hz, 1H), 1.76 (dd, J=24.1, 11.0 Hz, 1H), 1.46-1.34 (m, 1H), 1.25 (t, J=6.9 Hz, 6H); ESI MS m/z=414.2 (M+1)

Workup

  1. filtrationThe reaction mixture was filtered through Celite
  2. concentrationThe filtrate was concentrated

Sources & evidence

ORD record
ord-af0710698bd244e08cae3cb05b77dec3
Source dataset
uspto-grants-2016_02
Patent number
US09260425B2

Reaction notes

Loading…