3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine → 3-(1-(piperidin-4-ylmethyl)-1H-pyrazol-4-yl)-5-(pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridine

HRID 1775011Notes

Reaction equation

HRID 1775011 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:10](I)=[N:9][N:8](C3CCCCO3)[C:5]2=[CH:6][N:7]=1.CC1(C)C(C)(C)OB([C:26]2[CH:27]=[N:28][N:29]([CH:31]3[CH2:36][CH2:35]N(C(OC(C)(C)C)=O)CC3)[CH:30]=2)O1.[N:45]1[CH:50]=[CH:49][CH:48]=[C:47](B2OC(C)(C)C(C)(C)O2)[CH:46]=1>>[NH:7]1[CH2:6][CH2:35][CH:36]([CH2:31][N:29]2[CH:30]=[C:26]([C:10]3[C:4]4[C:5](=[CH:6][N:7]=[C:2]([C:49]5[CH:50]=[N:45][CH:46]=[CH:47][CH:48]=5)[CH:3]=4)[NH:8][N:9]=3)[CH:27]=[N:28]2)[CH2:3][CH2:2]1

Participants

4

Reactant 3

HCID 27346563-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 45480279tert-butyl 4-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]piperidine-1-carboxylateHCID 726984825-bromo-3-iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridine

Product 1

HCID 712541473-(1-(piperidin-4-ylmethyl)-1H-pyrazol-4-yl)-5-(pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridineYield 14%

Procedure

Following the Suzuki coupling procedure of Example 159, 5-bromo-3-iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridine and tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate were reacted. The product was subsequently reacted with 3-pyridineboronic acid pinacol ester by the Suzuki coupling procedure of Example 10 and deprotected by the procedure of Example 229. The mixture was purified via reverse phase HPLC using a gradient of MeOH in water with 0.1% NH4OH to afford 25 mg (14%) of 186 over three steps. ESI MS m/z 360.1 (M+1). 1H NMR (400 MHz, DMSO) 9.44 (d, J=2.1 Hz, 1H), 9.15 (d, J=1.0 Hz, 1H), 8.64-8.54 (m, 4H), 8.17 (s, 1H), 7.53 (dd, J=8.0, 4.8 Hz, 1H), 4.08 (d, J=7.2 Hz, 2H), 2.91 (d, J=12.0 Hz, 2H), 2.41 (t, J=10.9 Hz, 2H), 1.98 (s, 1H), 1.45 (d, J=11.2 Hz, 2H), 1.18-1.05 (m, 2H)

Workup

  1. customwere reacted
  2. customThe mixture was purified via reverse phase HPLC

Sources & evidence

ORD record
ord-ffdebc96f93049b3921b8e50908157ad
Source dataset
uspto-grants-2016_02
Patent number
US09260425B2

Reaction notes

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