Potassium Carbonate → ethyl {4-[7-amino-2-(isoquinolin-5-yl)furo[2,3-c]pyridin-4-yl]-1H-pyrazol-1-yl}acetate

HRID 389499Notes

Reaction equation

[CH:1]1[C:10]2[CH:9]=[CH:8][CH:7]=[C:6](B(O)O)[C:5]=2[CH:4]=[CH:3][N:2]=1.[CH2:14]([O:16][C:17](=[O:35])[CH2:18][N:19]1[CH:23]=[C:22]([C:24]2[CH:29]=[N:28][C:27]([NH2:30])=[C:26]3[O:31][C:32](Cl)=[CH:33][C:25]=23)[CH:21]=[N:20]1)[CH3:15].C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O>[NH2:30][C:27]1[N:28]=[CH:29][C:24]([C:22]2[CH:21]=[N:20][N:19]([CH2:18][C:17]([O:16][CH2:14][CH3:15])=[O:35])[CH:23]=2)=[C:25]2[CH:33]=[C:32]([C:6]3[CH:7]=[CH:8][CH:9]=[C:10]4[C:5]=3[CH:4]=[CH:3][N:2]=[CH:1]4)[O:31][C:26]=12

Participants

Conditions

Temperature: 100 °C

Procedure

A solution of isoquinoline-5-boronic acid (53.9 mg, 0.312 mmol) and ethyl[4-(7-amino-2-chlorofuro[2,3-c]pyridin-4-yl)-1H-pyrazol-1-yl]acetate (50.0 mg, 0.156 mol) in 1,4-dioxane (0.85 mL) and H2O (0.3 mL) was charged with potassium carbonate (32 mg, 0.23 mmol) and (1,1′-bis(diphenylphosphino)ferrocene)palladium dichloride (1 mg, 0.002 mmol) under an atmosphere of nitrogen. The mixture was heated in a microwave reactor at 100° C. for 40 min. Purification of the residue by flash chromatography (0 to 5% 7 N NH3/MeOH:EtOAc) afforded 27 mg (41%) of the title compound. 1H NMR (400 MHz, CD3OD) δ 9.36 (s, 1H), 8.57-8.63 (m, 1H), 8.52 (d, J=6.06 Hz, 1H), 8.37 (d, J=7.33 Hz, 1H), 8.27 (d, J=8.08 Hz, 1H), 8.18 (s, 1H), 7.98 (d, J=7.58 Hz, 2H), 7.85 (t, J=7.83 Hz, 1H), 7.55-7.62 (m, 1H), 7.53 (s, 1H), 4.28 (q, J=7.16 Hz, 2 H), 1.95 (s, 2H), 1.32 (t, 3H); MS (ESI): 415.16 [M+H]+; HPLC tR=0.94 min (TOF: polar—3 min).

Workup

customPurification of the residue by flash chromatography (0 to 5% 7 N NH3/MeOH:EtOAc)

Sources & evidence

ORD record: ord-70bd4764c74c494ea25974bedc29e6fb
Source dataset: uspto-grants-2013_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08378104B2

Reaction notes

Loading…