HCID 86676703, compound → HCID 71253627, compound

HRID 1775116Notes

Reaction equation

HRID 1775116 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2[CH:8]=[C:9]3[C:15]([C:16]4[N:21]=[C:20]([N:22]5[CH2:27][CH2:26][CH2:25][C@H:24]([NH:28][C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32])[CH2:23]5)[C:19]([CH:36]=[CH2:37])=[CH:18][CH:17]=4)=[N:14][N:13]([CH2:38][O:39][CH2:40][CH2:41][Si:42]([CH3:45])([CH3:44])[CH3:43])[C:10]3=[CH:11][N:12]=2)[CH:2]=1.[H][H]>C(O)C.[OH-].[OH-].[Pd+2]>[CH2:36]([C:19]1[C:20]([N:22]2[CH2:27][CH2:26][CH2:25][C@H:24]([NH:28][C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32])[CH2:23]2)=[N:21][C:16]([C:15]2[C:9]3[C:10](=[CH:11][N:12]=[C:7]([C:3]4[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=4)[CH:8]=3)[N:13]([CH2:38][O:39][CH2:40][CH2:41][Si:42]([CH3:45])([CH3:44])[CH3:43])[N:14]=2)=[CH:17][CH:18]=1)[CH3:37]

Participants

5

Reactant 2

HCID 86676703HCID 86676703, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 71253627HCID 71253627, compound

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 702EthanolSolvent

Procedure

(S)-tert-butyl 1-(6-(5-(pyridin-3-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-3-vinylpyridin-2-yl)piperidin-3-ylcarbamate (59.18 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-ethyl-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 mmol). 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 327 as an off-white solid (5.8 mg, 15%) over two steps. 1H NMR (400 MHz, DMSO) δ 9.31 (s, 1H), 9.20 (s, 1H), 9.13 (s, 1H), 8.59 (d, J=4.5 Hz, 1H), 8.46 (d, J=8.0 Hz, 1H), 7.81 (d, J=7.8 Hz, 1H), 7.71 (d, J=7.8 Hz, 1H), 7.53 (dd, J=8.0, 4.8 Hz, 1H), 3.60 (d, J=11.4 Hz, 2H), 2.86 (dt, J=20.8, 9.5 Hz, 2H), 2.70 (dd, J=18.0, 10.0 Hz, 2H), 1.95 (d, J=12.5 Hz, 1H), 1.84 (d, J=13.1 Hz, 1H), 1.80-1.69 (m, 1H), 1.26 (t, J=7.5 Hz, 3H); ESI MS m/z=400.2 (M+1)

Workup

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

Sources & evidence

ORD record
ord-16fa37a27b2d4dcf97dab7bb1020e78e
Source dataset
uspto-grants-2016_02
Patent number
US09260425B2

Reaction notes

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