Acetyl chloride → 2-((3-(4-(1-Acetylazetidin-3-yl)piperazin-1-yl)-2-chloro-5-cyanophenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile

HRID 921822Notes

Reaction equation

HRID 921822 reaction equation
[NH:1]1[CH2:4][CH:3]([N:5]2[CH2:10][CH2:9][N:8]([C:11]3[C:12]([Cl:44])=[C:13]([NH:19][C:20]4[N:25]=[C:24]([N:26]([CH:36]5[CH2:38][CH2:37]5)[CH2:27][C:28]5[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][CH:29]=5)[C:23]5=[N:39][CH:40]=[C:41]([C:42]#[N:43])[N:22]5[N:21]=4)[CH:14]=[C:15]([C:17]#[N:18])[CH:16]=3)[CH2:7][CH2:6]2)[CH2:2]1.[C:45](Cl)(=[O:47])[CH3:46].C(=O)(O)[O-].[Na+]>C(Cl)Cl>[C:45]([N:1]1[CH2:4][CH:3]([N:5]2[CH2:10][CH2:9][N:8]([C:11]3[C:12]([Cl:44])=[C:13]([NH:19][C:20]4[N:25]=[C:24]([N:26]([CH:36]5[CH2:37][CH2:38]5)[CH2:27][C:28]5[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][CH:29]=5)[C:23]5=[N:39][CH:40]=[C:41]([C:42]#[N:43])[N:22]5[N:21]=4)[CH:14]=[C:15]([C:17]#[N:18])[CH:16]=3)[CH2:7][CH2:6]2)[CH2:2]1)(=[O:47])[CH3:46]

Participants

5

Reactant 3

HCID 6367Acetyl chlorideHCID 516892Sodium BicarbonateHCID 899231462-((3-(4-(Azetidin-3-yl)piperazin-1-yl)-2-chloro-5-cyanophenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile

Product 1

HCID 1182533432-((3-(4-(1-Acetylazetidin-3-yl)piperazin-1-yl)-2-chloro-5-cyanophenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrileYield 102.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 2-((3-(4-(azetidin-3-yl)piperazin-1-yl)-2-chloro-5-cyanophenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (100 mg, 0.164 mmol) in DCM (1.0 mL) was added TEA (0.069 mL, 0.492 mmol) followed by acetyl chloride (0.014 mL, 0.197 mmol) in a drop wise manner. The reaction mixture was allowed to warm to room temperature and stirred for overnight. The reaction mixture was diluted with dichloromethane (50 mL) and poured into a separating funnel containing saturated aqueous sodium bicarbonate (10 mL). The aqueous layer was extracted with dichloromethane (2×50 mL). The combined organics were washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated under vacuum. The crude material was precipitated from DCM/Hexane (Dissolved in minimum amount of DCM, precipitated by adding Hexane), filtered and dried to get the 2-((3-(4-(1-acetylazetidin-3-yl)piperazin-1-yl)-2-chloro-5-cyanophenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (110 mg) as a off white solid.

Workup

  1. additionpoured into a separating funnel
  2. extractionThe aqueous layer was extracted with dichloromethane (2×50 mL)
  3. washThe combined organics were washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customThe crude material was precipitated from DCM/Hexane (Dissolved in minimum amount of DCM, precipitated by adding Hexane)
  8. filtrationfiltered
  9. customdried

Sources & evidence

ORD record
ord-89922953359b4721a68db60f921f8548
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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