Trifluoroacetic acid → HCID 86708642, compound

HRID 921761Notes

Reaction equation

HRID 921761 reaction equation
[C:1]([C:3]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([NH:12][C:13]3[N:18]=[C:17]([N:19](CC)[CH2:20][C:21]4C=CC(OC)=CC=4)[C:16]4=[N:31][CH:32]=[C:33]([C:34]#[N:35])[N:15]4[N:14]=3)[CH:10]=2)[N:5]([CH:36]2[CH2:41][CH2:40][N:39](C(OC(C)(C)C)=O)[CH2:38][CH2:37]2)[CH:4]=1)#[N:2].[C:49]1([O:55]C)[CH:54]=CC=C[CH:50]=1.C(O)(C(F)(F)F)=O>ClCCCl>[C:1]([C:3]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([NH:12][C:13]3[N:18]=[C:17]([NH:19][CH2:20][CH3:21])[C:16]4=[N:31][CH:32]=[C:33]([C:34]#[N:35])[N:15]4[N:14]=3)[CH:10]=2)[N:5]([CH:36]2[CH2:41][CH2:40][N:39]([CH2:50][C@@H:49]([OH:55])[CH3:54])[CH2:38][CH2:37]2)[CH:4]=1)#[N:2]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 7519AnisoleHCID 86708643HCID 86708643, compound

Product 1

HCID 86708642HCID 86708642, compound

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
25 °C

Procedure

tert-butyl 4-(3-cyano-5-((7-cyano-4-(ethyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)-1H-indol-1-yl)piperidine-1-carboxylate (500 mg, 0.503 mmol) was mixed with anisole (0.5 mL, 4.58 mmol) and DCE (5 mL). TFA (1 mL, 12.98 mmol) was added. The mixture was stirred at 25° C. for 24 hrs. LC/MS showed product formation. The mixture was concentrated to dryness, diluted with MeOH and applied onto a cartridge of Phenomenex Strata-X-C 33 um cation mixed-mode polymer. This was washed with methanol and product was eluted with 2 N solution of ammonia in methanol. Removal of the solvents left 2-((3-cyano-1-(piperidin-4-yl)-1H-indol-5-yl)amino)-4-(ethylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (80 mg) as solid.

Workup

  1. concentrationThe mixture was concentrated to dryness
  2. additiondiluted with MeOH
  3. additionmixed-mode polymer
  4. washThis was washed with methanol and product
  5. washwas eluted with 2 N solution of ammonia in methanol
  6. customRemoval of the solvents
  7. waitleft 2-((3-cyano-1-(piperidin-4-yl)-1H-indol-5-yl)amino)-4-(ethylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (80 mg) as solid

Sources & evidence

ORD record
ord-2192b8535fd44c8fac27b2e1a379b46a
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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