HCID 58464828, compound → HCID 86676695, compound

HRID 1775060Notes

Reaction equation

HRID 1775060 reaction equation
F[C:2]1[N:7]=[C:6]([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]([CH:23]3[CH2:28][CH2:27][CH2:26][CH2:25][O:24]3)[N:9]=2)[CH:5]=[CH:4][CH:3]=1.[NH:29]1[CH2:35][CH2:34][CH2:33][C@@H:32]([NH:36][C:37](=[O:46])[O:38][CH2:39][C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[CH2:31][CH2:30]1>CS(C)=O>[N:19]1[CH:20]=[CH:21][CH:22]=[C:17]([C:14]2[CH:15]=[C:16]3[C:8]([C:6]4[N:7]=[C:2]([N:29]5[CH2:35][CH2:34][CH2:33][C@@H:32]([NH:36][C:37](=[O:46])[O:38][CH2:39][C:40]6[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=6)[CH2:31][CH2:30]5)[CH:3]=[CH:4][CH:5]=4)=[N:9][N:10]([CH:23]4[CH2:28][CH2:27][CH2:26][CH2:25][O:24]4)[C:11]3=[CH:12][N:13]=2)[CH:18]=1

Participants

4

Reactant 2

HCID 58464828HCID 58464828, compoundHCID 712536623-(6-Fluoropyridin-2-yl)-5-(pyridin-3-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridine

Product 1

HCID 86676695HCID 86676695, compound

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
95 °C

Procedure

A solution containing 3-(6-fluoropyridin-2-yl)-5-(pyridin-3-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridine (0.075 g, 0.20 mmol) and (R)-benzyl azepan-4-ylcarbamate (0.298 g, 1.20 mmol) in Dimethyl sulfoxide (1.20 mL) was heated at 95° C. for 18 h. The reaction was quenched with water and then extracted with EtOAc 2×. The combined organic layer was dried with Na2SO4, filtered and concentrated. The crude product was dried under high vacuum overnight to give benzyl (4R)-1-(6-(5-(pyridin-3-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)pyridin-2-yl)azepan-4-ylcarbamate which was dissolved in Methylene chloride (2.56 mL) at −10° C. and treated with slowly with 1.00 M of Boron tribromide in Methylene chloride (0.600 mL). The reaction was stirred at RT for 7 h. The mixture was concentrated. The crude product was diluted in water and washed with EtOAc. The aqueous layer was basified to pH 11 then extracted with EtOAc. The combined organic layers was dried Na2SO4, filtered, and concentrated. The crude product was submitted for rHPLC to give 249 (21 mg, 27% yield). ESI MS m/z=386.1 (M+1). 1H NMR (500 MHz, DMSO) δ 9.21 (d, J=12.7 Hz, 2H), 8.96 (s, 1H), 8.59 (d, J=3.8 Hz, 1H), 8.38 (d, J=7.6 Hz, 1H), 7.61 (t, J=7.6 Hz, 1H), 7.58-7.51 (m, 1H), 7.42 (d, J=7.3 Hz, 1H), 6.62 (d, J=8.2 Hz, 1H), 4.00-3.78 (m, 2H), 3.76-3.57 (m, 2H), 2.89 (s, 1H), 2.00 (d, J=30.7 Hz, 2H), 1.85-1.55 (m, 3H), 1.44-1.31 (m, 1H)

Workup

  1. customThe reaction was quenched with water
  2. extractionextracted with EtOAc 2×
  3. dry with materialThe combined organic layer was dried with Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. dry with materialThe crude product was dried under high vacuum overnight

Sources & evidence

ORD record
ord-6f1d3b1a31454e82802ed0a286857916
Source dataset
uspto-grants-2016_02
Patent number
US09260425B2

Reaction notes

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