Methylamine → (R)-5-cyclopentyl-4-ethyl-N-methyl-4,5-dihydro-[1,2,4]triazolo[4,3-f]pteridin-7-amine

HRID 39344Notes

Reaction equation

Cl[C:2]1[N:11]=[CH:10][C:9]2[N:8]3[CH:12]=[N:13][N:14]=[C:7]3[C@@H:6]([CH2:15][CH3:16])[N:5]([CH:17]3[CH2:21][CH2:20][CH2:19][CH2:18]3)[C:4]=2[N:3]=1.[CH3:22][NH2:23].C(O)(C(F)(F)F)=O.C(=O)([O-])[O-]>C(O)C.C(#N)C.O>[CH:17]1([N:5]2[C:4]3[N:3]=[C:2]([NH:23][CH3:22])[N:11]=[CH:10][C:9]=3[N:8]3[CH:12]=[N:13][N:14]=[C:7]3[C@H:6]2[CH2:15][CH3:16])[CH2:21][CH2:20][CH2:19][CH2:18]1

Participants

Conditions

Temperature: 50 °C

Procedure

In a vial containing (R)-7-chloro-5-cyclopentyl-4-ethyl-4,5-dihydro-[1,2,4]triazolo[4,3-f]pteridine (70 mg, 0.23 mmol) was added a solution of methylamine in ethanol (2 mL, 2M soln.) The vessel was sealed then heated at 50° C. for 18 hours. After cooling, the solvent was removed under reduced pressure and the crude product was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 M, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]. The free base was obtained by passing the TFA salt in acetonitrile/water through a carbonate cartridge to afford the title compound as a white powder (42 mg, 61% yield).

Workup

customwas sealed
temperatureAfter cooling
customthe solvent was removed under reduced pressure
customthe crude product was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 M, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]
customThe free base was obtained

Sources & evidence

ORD record: ord-e9d3f5a185254435852a078380e36718
Source dataset: uspto-grants-2013_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08524902B2

Reaction notes

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