Trifluoroacetic acid → (+/-)-2-((2-chloro-5-cyano-3-((4aR,8aR)-hexahydro-1H-pyrido[3,4-b][1,4]oxazin-6(7H)-yl)phenyl)amino)-4-(ethylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile

HRID 921733Notes

Reaction equation

[Cl:1][C:2]1[C:7]([NH:8][C:9]2[N:14]=[C:13]([N:15](CC)[CH2:16][C:17]3C=CC(OC)=CC=3)[C:12]3=[N:27][CH:28]=[C:29]([C:30]#[N:31])[N:11]3[N:10]=2)=[CH:6][C:5]([C:32]#[N:33])=[CH:4][C:3]=1[N:34]1[CH2:43][CH2:42][C@@H:41]2[C@H:36]([O:37][CH2:38][CH2:39][N:40]2C(OC(C)(C)C)=O)[CH2:35]1.C1(OC)C=CC=CC=1.C(O)(C(F)(F)F)=O>ClCCCl>[Cl:1][C:2]1[C:3]([N:34]2[CH2:43][CH2:42][C@@H:41]3[C@H:36]([O:37][CH2:38][CH2:39][NH:40]3)[CH2:35]2)=[CH:4][C:5]([C:32]#[N:33])=[CH:6][C:7]=1[NH:8][C:9]1[N:14]=[C:13]([NH:15][CH2:16][CH3:17])[C:12]2=[N:27][CH:28]=[C:29]([C:30]#[N:31])[N:11]2[N:10]=1

Participants

Conditions

Temperature: 25 °C

Procedure

(+/−)-(4aR,8aR)-tert-butyl 6-(2-chloro-5-cyano-3-((7-cyano-4-(ethyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)octahydro-1H-pyrido[3,4-b][1,4]oxazine-1-carboxylate (75 mg, 0.104 mmol) was taken up in DCE (2 mL), anisole (0.05 mL, 0.458 mmol) and TFA (0.5 mL, 6.49 mmol). The mixture stirred 2 h at 25° C. and solvents removed. 50 ml 2N NH3/MeOH was added and stirred for 30 min. The white precipitate was collected by filtration and washed with 20 ml cold MeOH, then ether and dried under air-suction for 2 hrs to give (+/−)-2-((2-chloro-5-cyano-3-((4aR,8aR)-hexahydro-1H-pyrido[3,4-b][1,4]oxazin-6(7H)-yl)phenyl)amino)-4-(ethylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (38 mg).

Workup

customsolvents removed
addition50 ml 2N NH3/MeOH was added
stirringstirred for 30 min
filtrationThe white precipitate was collected by filtration
washwashed with 20 ml cold MeOH
dry with materialether and dried under air-suction for 2 hrs

Sources & evidence

ORD record: ord-7917b6a06d57403c9373cc5d8258c21a
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09273057B2

Reaction notes

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