Trifluoroacetic acid → HCID 89923044, compound

HRID 921882Notes

Reaction equation

HRID 921882 reaction equation
[Cl:1][C:2]1[C:7]([NH:8][CH2:9][CH2:10][CH2:11][OH:12])=[CH:6][C:5]([C:13]#[N:14])=[CH:4][C:3]=1[NH:15][C:16]1[N:21]=[C:20]([N:22]([CH:32]2[CH2:34][CH2:33]2)CC2C=CC(OC)=CC=2)[C:19]2=[N:35][CH:36]=[C:37]([C:38]#[N:39])[N:18]2[N:17]=1.CCN(C(C)C)C(C)C.Cl[C:50](Cl)([O:52]C(=O)OC(Cl)(Cl)Cl)Cl.C(O)(C(F)(F)F)=O>ClC(Cl)C.C1(OC)C=CC=CC=1>[Cl:1][C:2]1[C:7]([N:8]2[CH2:9][CH2:10][CH2:11][O:12][C:50]2=[O:52])=[CH:6][C:5]([C:13]#[N:14])=[CH:4][C:3]=1[NH:15][C:16]1[N:21]=[C:20]([NH:22][CH:32]2[CH2:33][CH2:34]2)[C:19]2=[N:35][CH:36]=[C:37]([C:38]#[N:39])[N:18]2[N:17]=1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 89923012HCID 89923012, compound

Product 1

HCID 89923044HCID 89923044, compoundYield 33.3%

Reagents, catalysts & solvents 2

HCID 7519AnisoleCatalystHCID 63651,1-DichloroethaneSolvent2×

Procedure

To a solution of 2-((2-chloro-5-cyano-3-((3-hydroxypropyl)amino)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (15 mg, 0.028 mmol) in dichloroethane (1 mL) was added Hunig's Base (0.048 mL, 0.276 mmol) followed by triphosgene (40.9 mg, 0.138 mmol). After stirring at room temperature for 1 h, LC-MS indicated the desired peak. After concentration, purification via flash chromatography (0-10% MeOH in DCM, 12 g) gave 15 mg of the PMB protected product. This was dissolved in 1 mL of dichloroethane and then 1 drop of anisole was added followed by 0.5 mL of TFA. The solution was heated at 60° C. for 1 h. LC-MS indicated completion, and then it was cooled and concentrated. The crude was dissolved in methanol and neutralized with 7N ammonia in methanol. After stirring for 10 min it was concentrated, purification via preparative HPLC gave the title compound as a yellow solid (4.2 mg).

Workup

  1. concentrationAfter concentration, purification via flash chromatography (0-10% MeOH in DCM, 12 g)
  2. customgave 15 mg of the PMB
  3. temperatureThe solution was heated at 60° C. for 1 h
  4. temperatureit was cooled
  5. concentrationconcentrated
  6. dissolutionThe crude was dissolved in methanol and neutralized with 7N ammonia in methanol
  7. stirringAfter stirring for 10 min it
  8. concentrationwas concentrated
  9. custompurification via preparative HPLC

Sources & evidence

ORD record
ord-6bd1fbda14c54080a60da36af857c869
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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