Acetic Acid → HCID 89922670, compound

HRID 921843Notes

Reaction equation

HRID 921843 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([CH2:8][CH2:9][CH2:10][CH:11]=O)[C:5]([C:13]#[N:14])=[CH:4][C:3]=1[NH:15][C:16]1[N:21]=[C:20]([N:22]([CH:32]2[CH2:34][CH2:33]2)[CH2:23][C:24]2[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=2)[C:19]2=[N:35][CH:36]=[C:37]([C:38]#[N:39])[N:18]2[N:17]=1.[CH3:40][O:41][CH:42]1[CH2:45][NH:44][CH2:43]1.CC(O)=O.C([BH3-])#N.[Na+]>C1COCC1.CO.CCOC(C)=O>[Cl:1][C:2]1[CH:7]=[C:6]([CH2:8][CH2:9][CH2:10][CH2:11][N:44]2[CH2:45][CH:42]([O:41][CH3:40])[CH2:43]2)[C:5]([C:13]#[N:14])=[CH:4][C:3]=1[NH:15][C:16]1[N:21]=[C:20]([N:22]([CH:32]2[CH2:33][CH2:34]2)[CH2:23][C:24]2[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=2)[C:19]2=[N:35][CH:36]=[C:37]([C:38]#[N:39])[N:18]2[N:17]=1

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 5003444Sodium cyanoborohydrideHCID 134019963-MethoxyazetidineHCID 89922850HCID 89922850, compound

Product 1

HCID 89922670HCID 89922670, compoundYield 47.8%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

2-((2-chloro-5-cyano-4-(4-oxobutyl)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (22 mg, 0.041 mmol) was taken up in THF (0.3 mL) and a solution of 3-methoxyazetidine (5.31 mg, 0.061 mmol) in MeOH (0.1 mL) was added, followed by a drop of AcOH and sodium cyanoborohydride (5.11 mg, 0.081 mmol). The reaction was stirred at room temperature for 1 h. The reaction was diluted with EtOAc and washed with water, then brine. The organic layer was dried over Na2SO4, filtered, and concentrated. The material was purified by flash column chromatography (0-7% MeOH/DCM; 24 g column). 2-((2-chloro-5-cyano-4-(4-(3-methoxyazetidin-1-yl)butyl)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (12 mg) was obtained as a yellow glass.

Workup

  1. washwashed with water
  2. dry with materialThe organic layer was dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe material was purified by flash column chromatography (0-7% MeOH/DCM; 24 g column)

Sources & evidence

ORD record
ord-6bab8827a8f045be95d1aaa660a352db
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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