Hydrochloric Acid → 4-((R)-5-cyclopentyl-4-ethyl-4,5-dihydro-[1,2,4]triazolo[4,3-f]pteridin-7-ylamino)-3-methoxy-N-methylbenzamide

HRID 476133Notes

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.[NH2:22][C:23]1[CH:32]=[CH:31][C:26]([C:27]([NH:29][CH3:30])=[O:28])=[CH:25][C:24]=1[O:33][CH3:34].Cl.C([O-])(O)=O.[Na+]>C(O)C.O>[CH:17]1([N:5]2[C:4]3[N:3]=[C:2]([NH:22][C:23]4[CH:32]=[CH:31][C:26]([C:27]([NH:29][CH3:30])=[O:28])=[CH:25][C:24]=4[O:33][CH3:34])[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: 90 °C

Procedure

To a solution of (R)-7-chloro-5-cyclopentyl-4-ethyl-4,5-dihydro-[1,2,4]triazolo[4,3-f]pteridine (80 mg, 0.263 mmol) in a mixture ethanol/water (1/4, 5 mL) were added 4-amino-3-methoxy-N-methylbenzamide (72 mg, 0.394 mmol) followed by a catalytic amount of concentrated HCl (0.04 mL). The reaction mixture was stirred at 90° C. for 24 hours, then cooled to room temperature and basified with saturated aqueous solution of NaHCO3. The mixture was extracted with ethyl acetate, the organic layer was dried (MgSO4) and the residue purified by flash chromatography to give the title compound as a colourless solid (92 mg, 78% yield); 1H NMR (DMSO D6) 0.75 (3H, t), 1.43-1.60 (4H, m), 1.80-2.07 (6H, m), 2.80 (3H, d), 3.88 (3H, s), 4.19 (1H, m), 5.38 (1H, m), 7.50 (1H, d), 7.59 (1H, s), 7.83 (1H, d), 8.47 (1H, m), 8.67 (1H, s), 9.31 (1H, s), 9.40 (1H, br s); LC/MS M+1 (obs.) 449.3.

Workup

extractionThe mixture was extracted with ethyl acetate
dry with materialthe organic layer was dried (MgSO4)
customthe residue purified by flash chromatography

Sources & evidence

ORD record: ord-dc8eec947ea346fea60c876cd543c9b6
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08637666B2

Reaction notes

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