3-methyl-1-(oxan-4-yl)-1H-pyrazol-5-amine → Ethyl 6-cyclopropyl-3-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylate

HRID 476047Notes

Reaction equation

[CH3:1][C:2]1[CH:6]=[C:5]([NH2:7])[N:4]([CH:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[N:3]=1.[CH:14]1(/[C:17](/O)=[CH:18]/[C:19](=O)[C:20]([O:22][CH2:23][CH3:24])=[O:21])[CH2:16][CH2:15]1>C(O)(=O)C>[CH:14]1([C:17]2[CH:18]=[C:19]([C:20]([O:22][CH2:23][CH3:24])=[O:21])[C:6]3[C:2]([CH3:1])=[N:3][N:4]([CH:8]4[CH2:13][CH2:12][O:11][CH2:10][CH2:9]4)[C:5]=3[N:7]=2)[CH2:15][CH2:16]1

Participants

Conditions

Temperature: 117 °C

Procedure

A mixture of 3-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-5-amine (380 mg, 2.097 mmol), ethyl (3Z)-4-cyclopropyl-4-hydroxy-2-oxo-3-butenoate (386 mg, 2.097 mmol) and acetic acid (50 mL) were heated at 117° C. for 2 hours. The solvent was removed in vacuo, and the crude residue was purified via silica gel chromatography (eluent: 0 to 25% EtOAc:Hex). The desired product was collected as a solid, 300 mg (43%). LCMS E-S (M+H)=330.3 1H NMR (400 MHz, DMSO-d6) δ ppm 1.00-1.12 (m, 4H), 1.37 (t, J=7.20 Hz, 3H), 1.82 (dd, J=12.51, 2.40 Hz, 2H), 2.16 (qd, J=12.21, 4.55 Hz, 2H), 2.29-2.42 (m, 1H), 2.54 (s, 3H), 3.47-3.60 (m, 2H), 3.99 (dd, J=11.37, 3.79 Hz, 2H), 4.42 (q, J=7.24 Hz, 2H), 4.92 (tt, J=11.59, 4.20 Hz, 1H), 7.46 (s, 1H).

Workup

customThe solvent was removed in vacuo
customthe crude residue was purified via silica gel chromatography (eluent: 0 to 25% EtOAc:Hex)
customThe desired product was collected as a solid, 300 mg (43%)

Sources & evidence

ORD record: ord-a322060191fd4f449a578cd2bb1322c0
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08637509B2

Reaction notes

Loading…