HCID 178493980, compound → HCID 178493981, compound

HRID 707357Notes

Reaction equation

HRID 707357 reaction equation
Cl[C:2]1[CH:11]=[C:10]2[C:5]([N:6]=[CH:7][C:8]([NH:12][C@H:13]3[CH2:16][C@H:15]([N:17]4[C:21]5=[N:22][CH:23]=[CH:24][CH:25]=[C:20]5[N:19]=[C:18]4[O:26][CH3:27])[CH2:14]3)=[N:9]2)=[CH:4][CH:3]=1>[Pd].CO>[CH3:27][O:26][C:18]1[N:17]([C@H:15]2[CH2:16][C@H:13]([NH:12][C:8]3[CH2:7][NH:6][C:5]4[C:10](=[CH:11][CH:2]=[CH:3][CH:4]=4)[N:9]=3)[CH2:14]2)[C:21]2=[N:22][CH:23]=[CH:24][CH:25]=[C:20]2[N:19]=1

Participants

4

Reactant 1

HCID 178493980HCID 178493980, compound

Product 1

HCID 178493981HCID 178493981, compoundYield 74.2%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

To a 15-mL round-bottomed flask was added 7-chloro-N-(−3-(2-methoxy-3H-imidazo[4,5-b]pyridin-3-yl)cyclobutyl)quinoxalin-2-amine (example 19, 118 mg, 0.310 mmol) and palladium on activated carbon (10 wt. %, 33.0 μl, 0.310 mmol) in methanol. The reaction mixture was stirred under a hydrogen balloon for 3 days. The solution was filtered and concentrated in vacuo to give the crude material as a yellow oil. The crude material was absorbed onto a plug of silica gel and purified by chromatography through a Redi-Sep pre-packed silica gel column (4 g, 0-20% (2M ammonia in methanol) in dichloromethane gradient) to provide N-(trans-3-(2-methoxy-3H-imidazo[4,5-b]pyridin-3-yl)cyclobutyl)-3,4-dihydroquinoxalin-2-amine (80 mg, 0.230 mmol, 74.1% yield) as light-yellow glass. M+1: 349.1. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.68 (br. s, 1 H) 2.52 (d, J=2.05 Hz, 2 H) 3.33-3.52 (m, 2 H) 3.81 (s, 2 H) 4.25 (s, 3 H) 4.68-4.81 (m, 1 H) 5.40 (quin, J=8.59 Hz, 1 H) 6.58 (dd, J=7.53, 1.39 Hz, 1 H) 6.76 (td, J=7.50, 1.60 Hz, 1 H) 6.84 (td, J=7.50, 1.60 Hz, 1 H) 7.05 (d, J=7.16 Hz, 1 H) 7.10 (dd, J=7.82, 5.04 Hz, 1 H) 7.75 (dd, J=7.82, 1.39 Hz, 1 H) 8.16 (dd, J=4.97, 1.46 Hz, 1 H).

Workup

  1. filtrationThe solution was filtered
  2. concentrationconcentrated in vacuo
  3. customto give the crude material as a yellow oil
  4. customThe crude material was absorbed onto a plug of silica gel
  5. custompurified by chromatography through a Redi-Sep pre-packed silica gel column (4 g, 0-20% (2M ammonia in methanol) in dichloromethane gradient)

Sources & evidence

ORD record
ord-42919780b8c747f1a8214c43816e6565
Source dataset
uspto-grants-2015_11
Patent number
US09174992B2

Reaction notes

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