Acetic Acid → HCID 89922683, compound

HRID 921849Notes

Reaction equation

HRID 921849 reaction equation
[Cl:1][C:2]1[C:7]([CH:8]([CH3:11])[CH:9]=O)=[CH:6][C:5]([C:12]#[N:13])=[CH:4][C:3]=1[NH:14][C:15]1[N:20]=[C:19]([N:21]([CH:31]2[CH2:33][CH2:32]2)[CH2:22][C:23]2[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=2)[C:18]2=[N:34][CH:35]=[C:36]([C:37]#[N:38])[N:17]2[N:16]=1.[NH:39]1[CH2:42][CH:41]([OH:43])[CH2:40]1.CC(O)=O.C([BH3-])#N.[Na+]>C1COCC1.CO.CCOC(C)=O>[Cl:1][C:2]1[C:7]([CH:8]([CH3:11])[CH2:9][N:39]2[CH2:42][CH:41]([OH:43])[CH2:40]2)=[CH:6][C:5]([C:12]#[N:13])=[CH:4][C:3]=1[NH:14][C:15]1[N:20]=[C:19]([N:21]([CH:31]2[CH2:33][CH2:32]2)[CH2:22][C:23]2[CH:24]=[CH:25][C:26]([O:29][CH3:30])=[CH:27][CH:28]=2)[C:18]2=[N:34][CH:35]=[C:36]([C:37]#[N:38])[N:17]2[N:16]=1

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 15142903-HydroxyazetidineHCID 5003444Sodium cyanoborohydrideHCID 89922524HCID 89922524, compound

Product 1

HCID 89922683HCID 89922683, compoundYield 63.7%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

2-((2-chloro-5-cyano-3-(1-oxopropan-2-yl)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (25 mg, 0.047 mmol) was taken up in THF (0.5 mL) and a solution of azetidin-3-ol (6.94 mg, 0.095 mmol) in MeOH (0.333 mL) was added. A drop of AcOH was added and the solution was stirred for 10 min. Next, sodium cyanoborohydride (5.96 mg, 0.095 mmol) was added and the reaction was stirred for 1 h. The reaction was diluted with EtOAc and washed with 2M K3PO4 solution. The organic layer was dried over Na2SO4, filtered, and concentrated. The material was purified by flash column chromatography (0-10% MeOHiDCM; 12 g column). 2-((2-chloro-5-cyano-3-(1-(3-hydroxyazetidin-1-yl)propan-2-yl)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (17.5 mg) was obtained as a yellow glass.

Workup

  1. stirringthe reaction was stirred for 1 h
  2. washwashed with 2M K3PO4 solution
  3. dry with materialThe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe material was purified by flash column chromatography (0-10% MeOHiDCM; 12 g column)

Sources & evidence

ORD record
ord-e91af04dda534781924aade702c596f0
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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