Ammonia → 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

HRID 921821Notes

Reaction equation

HRID 921821 reaction equation
[Cl:1][C:2]1[C:7]([NH:8][C:9]2[N:14]=[C:13]([N:15]([CH:25]3[CH2:27][CH2:26]3)[CH2:16][C:17]3[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=3)[C:12]3=[N:28][CH:29]=[C:30]([C:31]#[N:32])[N:11]3[N:10]=2)=[CH:6][C:5]([C:33]#[N:34])=[CH:4][C:3]=1[N:35]1[CH2:40][CH2:39][N:38]([CH:41]2[CH2:44][N:43](C(OC(C)(C)C)=O)[CH2:42]2)[CH2:37][CH2:36]1.N1C(C)=CC=CC=1C.[Si](OS(C(F)(F)F)(=O)=O)(C)(C)C.N>ClCCl>[NH:43]1[CH2:44][CH:41]([N:38]2[CH2:39][CH2:40][N:35]([C:3]3[C:2]([Cl:1])=[C:7]([NH:8][C:9]4[N:14]=[C:13]([N:15]([CH:25]5[CH2:26][CH2:27]5)[CH2:16][C:17]5[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=5)[C:12]5=[N:28][CH:29]=[C:30]([C:31]#[N:32])[N:11]5[N:10]=4)[CH:6]=[C:5]([C:33]#[N:34])[CH:4]=3)[CH2:36][CH2:37]2)[CH2:42]1

Participants

6

Reactant 4

HCID 222AmmoniaHCID 79372,6-LutidineHCID 65367Trimethylsilyl triflateHCID 89924048Tert-butyl 3-(4-(2-chloro-5-cyano-3-((7-cyano-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)piperazin-1-yl)azetidine-1-carboxylate

Product 1

HCID 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-carbonitrileYield 72.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of tert-butyl 3-(4-(2-chloro-5-cyano-3-((7-cyano-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)piperazin-1-yl)azetidine-1-carboxylate (400 mg, 0.563 mmol) in dichloromethane (4.0 mL) at 0° C., was added 2,6-lutidine (0.197 mL, 1.690 mmol). After that TMS-OTf (0.305 mL, 1.690 mmol) was added drop wise. The reaction mixture was allowed to warm to room temperature and stirred for 5 h. The reaction mixture was diluted with dichloromethane (50 mL) and poured into a separating funnel containing liquor ammonia (5 mL). The aqueous layer was extracted with dichloromethane (2×50 mL). The combined organic layer were washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crude material was washed with pentane (3×10 ml) and diethyl ether (3×5 mL). After the washing the resultant solid was dried under vacuum to get 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 (250 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 organic layer were washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. washThe crude material was washed with pentane (3×10 ml) and diethyl ether (3×5 mL)
  8. customAfter the washing the resultant solid was dried under vacuum

Sources & evidence

ORD record
ord-ae605cdd134842929d7c06aaa5368b9e
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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