(2S)-2-Methyloxirane → HCID 86708606, compound

HRID 921725Notes

Reaction equation

HRID 921725 reaction equation
[NH:1]1[CH2:4][CH:3]([C:5]2[C:6]([Cl:28])=[C:7]([NH:13][C:14]3[N:19]=[C:18]([NH:20][CH2:21][CH3:22])[C:17]4=[N:23][CH:24]=[C:25]([C:26]#[N:27])[N:16]4[N:15]=3)[CH:8]=[C:9]([C:11]#[N:12])[CH:10]=2)[CH2:2]1.[CH2:29]1[O:32][C@H:30]1[CH3:31]>CN1C(=O)CCC1.CO>[Cl:28][C:6]1[C:5]([CH:3]2[CH2:2][N:1]([CH2:29][C@@H:30]([OH:32])[CH3:31])[CH2:4]2)=[CH:10][C:9]([C:11]#[N:12])=[CH:8][C:7]=1[NH:13][C:14]1[N:19]=[C:18]([NH:20][CH2:21][CH3:22])[C:17]2=[N:23][CH:24]=[C:25]([C:26]#[N:27])[N:16]2[N:15]=1

Participants

5

Reactant 2

HCID 146262(2S)-2-MethyloxiraneHCID 86708607HCID 86708607, compound

Product 1

HCID 86708606HCID 86708606, compoundYield 32.9%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
50 °C

Procedure

A suspension of 2-((3-(azetidin-3-yl)-2-chloro-5-cyanophenyl)amino)-4-(ethylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (Example 367)(16 mg, 0.041 mmol) and (S)-(−)-propylene oxide (0.085 mL, 1.22 mmol) in a mixture of NMP (0.8 mL) and MeOH (0.2 mL) was stirred at 50° C. for 4.5 hr. The solvent was removed and the product was purified by preparative HPLC (Waters XBridge C18, 19×200 mm, 5-μm particles; Mobile Phase A: water with 20-mM ammonium acetate; Mobile Phase B: 95:5 acetonitrile: water with 20-mM ammonium acetate; Gradient: 15-55% B over 20 minutes, then a 5-minute hold at 100% B; Flow: 20 mL/min) to give the title compound (6.1 mg). This was converted to the mono HCl salt.

Workup

  1. customThe solvent was removed
  2. customthe product was purified by preparative HPLC (Waters XBridge C18, 19×200 mm, 5-μm particles
  3. waitGradient: 15-55% B over 20 minutes
  4. customa 5-minute hold

Sources & evidence

ORD record
ord-ca3cf582faa04b27bafb7bf512a1fadf
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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