Triethylamine → HCID 89923852, compound

HRID 921837Notes

Reaction equation

HRID 921837 reaction equation
CS(O[CH2:6][CH2:7][CH2:8][C:9]1[CH:14]=[C:13]([Cl:15])[C:12]([NH:16][C:17]2[N:22]=[C:21]([N:23]([CH:33]3[CH2:35][CH2:34]3)[CH2:24][C:25]3[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=3)[C:20]3=[N:36][CH:37]=[C:38]([C:39]#[N:40])[N:19]3[N:18]=2)=[CH:11][C:10]=1[C:41]#[N:42])(=O)=O.CCN(CC)CC.[NH:50]1[CH2:53][CH:52]([OH:54])[CH2:51]1>C(#N)C.CN(C=O)C.CCOC(C)=O>[Cl:15][C:13]1[CH:14]=[C:9]([CH2:8][CH2:7][CH2:6][N:50]2[CH2:53][CH:52]([OH:54])[CH2:51]2)[C:10]([C:41]#[N:42])=[CH:11][C:12]=1[NH:16][C:17]1[N:22]=[C:21]([N:23]([CH:33]2[CH2:35][CH2:34]2)[CH2:24][C:25]2[CH:26]=[CH:27][C:28]([O:31][CH3:32])=[CH:29][CH:30]=2)[C:20]2=[N:36][CH:37]=[C:38]([C:39]#[N:40])[N:19]2[N:18]=1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 15142903-HydroxyazetidineHCID 89923435HCID 89923435, compound

Product 1

HCID 89923852HCID 89923852, compoundYield 30.1%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

3-(5-chloro-2-cyano-4-((7-cyano-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)propyl methanesulfonate (45 mg, 0.074 mmol) was taken up in acetonitrile (1 mL) and Et3N (0.015 mL, 0.111 mmol) and azetidin-3-ol (6.50 mg, 0.089 mmol) were added. The reaction was heated at 60° C. overnight. A mixture of product and SM detected by LCMS. An additional 1.2 eq of amine in 0.2 ml of DMF was added, and the reaction was heated at 60° C. overnight. The reaction mixture was cooled to room temperature and diluted with EtOAc. The organic layer was washed 2× with water and once with brine, then dried over Na2SO4, filtered, and concentrated. The material was purified by flash column chromatography (0-10% MeOH/DCM; 24 g column). 2-((2-chloro-5-cyano-4-(3-(3-hydroxyazetidin-1-yl)propyl)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (13 mg) was obtained as a purple glass.

Workup

  1. additionA mixture of product and SM
  2. temperaturethe reaction was heated at 60° C. overnight
  3. temperatureThe reaction mixture was cooled to room temperature
  4. washThe organic layer was washed 2× with water
  5. dry with materialonce with brine, then dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe material was purified by flash column chromatography (0-10% MeOH/DCM; 24 g column)

Sources & evidence

ORD record
ord-4152ae73ed344160beaa4a7e0e2215cf
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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