2-Aminoisonicotinonitrile → HCID 66665217, compound

HRID 872309Notes

Reaction equation

HRID 872309 reaction equation
[C:1]([O:5][C:6](=[O:28])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18](=O)[CH:19](Br)[C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[NH2:29][C:30]1[CH:35]=[C:34]([C:36]#[N:37])[CH:33]=[CH:32][N:31]=1>C(O)C>[C:1]([O:5][C:6](=[O:28])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[N:29]=[C:30]4[CH:35]=[C:34]([C:36]#[N:37])[CH:33]=[CH:32][N:31]4[C:19]=3[C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 70155242-Aminoisonicotinonitrile2×HCID 86691038tert-Butyl (1-{4-[bromo(phenyl)acetyl]phenyl}cyclobutyl)carbamate

Product 1

HCID 66665217HCID 66665217, compoundYield 21.6%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of {1-[4-(2-bromo-2-phenyl-acetyl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester [Int-1-A] (2.65 g, 5.69 mmol), 2-amino-4-cyanopyridine (1.42 g, 11.9 mmol, 2 equiv) and powdered activated 3 Å molecular sieves (10 g) in ethanol (22 mL) was heated for 4 h at the reflux temperature. The reaction mixture was cooled to room temperature, additional 2-amino-4-cyanopyridine (0.71 g, 6.0 mmol, 1 equiv) was added, and the resulting mixture was heated at the reflux temperature for 5 h. The resulting solution was separated between EtOAc (75 mL) and an saturated aqueous NaHCO3 solution (75 mL). The organic phase was washed with a saturated aqueous NaCl solution (25 mL), dried (Na2SO4 anh), and concentrated under reduced pressure. The remaining material was purified using MPLC (Biotage Isolera; 25 g SNAP cartridge: 80% hexane/20% EtOAc for 3.0 min., gradient to 70% hexane/30% EtOAc over 13.7 min.) to give {1-[4-(7-cyano-3-phenyl-imidazo[1,2-a]pyridin-2-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester (0.57 g, 21%).

Workup

  1. temperaturewas heated for 4 h at the reflux temperature
  2. temperaturethe resulting mixture was heated at the reflux temperature for 5 h
  3. customThe resulting solution was separated between EtOAc (75 mL)
  4. washThe organic phase was washed with a saturated aqueous NaCl solution (25 mL)
  5. dry with materialdried (Na2SO4 anh)
  6. concentrationconcentrated under reduced pressure
  7. customThe remaining material was purified
  8. customMPLC (Biotage Isolera; 25 g SNAP cartridge: 80% hexane/20% EtOAc for 3.0 min., gradient to 70% hexane/30% EtOAc over 13.7 min.)

Sources & evidence

ORD record
ord-933a250b38164a74b6ddd904af0bab3f
Source dataset
uspto-grants-2015_03
Patent number
US08975265B2

Reaction notes

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