Diisopropylethylamine → Ethyl 1-ethyl-6-methyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridine-5-carboxylate

HRID 490903

Reaction equation

Cl.[NH2:2][CH:3]1[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1.Cl[C:10]1[C:15]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[C:14]([CH3:21])[N:13]=[C:12]2[N:22]([CH2:25][CH3:26])[N:23]=[CH:24][C:11]=12.C(N(CC)C(C)C)(C)C>C(#N)C>[CH2:25]([N:22]1[C:12]2=[N:13][C:14]([CH3:21])=[C:15]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[C:10]([NH:2][CH:3]3[CH2:8][CH2:7][O:6][CH2:5][CH2:4]3)=[C:11]2[CH:24]=[N:23]1)[CH3:26]

Participants

Conditions

Temperature: 85 °C

Procedure

4-Aminotetrahydropyran hydrochloride (Intermediate 21, 0.413 g, 3.0 mmol) was added to a mixture of Intermediate 58 (0.268 g, 1.0 mmol) and N,N-diisopropylethylamine (0.87 ml, 5.0 mmol) in acetonitrile (3 ml). The resulting mixture was heated at 85° C. for 24 hours. Volatiles were removed in vacuo and the residue was dissolved in chloroform (1.5 ml) and applied to a SPE cartridge (silica, 5 g). The cartridge was eluted successively with Et2O, EtOAc and EtOAc-MeOH (9/1). Fractions containing the desired product were combined and concentrated in vacuo to give the desired product contaminated with starting material (Intermediate 51). Further purification using a SPE cartridge (silica, 5 g) eluting with ethyl acetate-cyclohexane (1:3) afforded Intermediate 59 (0.248 g). LCMS showed MH+=333; TRET=2.75 min.

Workup

customVolatiles were removed in vacuo
dissolutionthe residue was dissolved in chloroform (1.5 ml)
washThe cartridge was eluted successively with Et2O, EtOAc and EtOAc-MeOH (9/1)
additionFractions containing the desired product
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-6d935c354da742dfa1536061aa83318d
Source dataset: uspto-grants-2009_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07528148B2

Linked notes

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