Phenol → 5-(8-Amino-3-cyclobutylimidazo[1,5-a]pyrazin-1-yl)-2-phenoxybenzonitrile

HRID 449071Notes

Reaction equation

[NH2:1][C:2]1[C:3]2[N:4]([C:8]([CH:20]3[CH2:23][CH2:22][CH2:21]3)=[N:9][C:10]=2[C:11]2[CH:12]=[CH:13][C:14](F)=[C:15]([CH:18]=2)[C:16]#[N:17])[CH:5]=[CH:6][N:7]=1.[C:24]1([OH:30])[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C(=O)([O-])[O-].[K+].[K+].CN(C=O)C>>[NH2:1][C:2]1[C:3]2[N:4]([C:8]([CH:20]3[CH2:23][CH2:22][CH2:21]3)=[N:9][C:10]=2[C:11]2[CH:12]=[CH:13][C:14]([O:30][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[C:15]([CH:18]=2)[C:16]#[N:17])[CH:5]=[CH:6][N:7]=1

Participants

Reactant 4

HCID 996Phenol

HCID 6228Dimethylformamide

HCID 11430Potassium Carbonate

HCID 669156655-(8-Amino-3-cyclobutylimidazo[1,5-a]pyrazin-1-yl)-2-fluorobenzonitrile

Product 1

HCID 579608205-(8-Amino-3-cyclobutylimidazo[1,5-a]pyrazin-1-yl)-2-phenoxybenzonitrileYield 29.9%

Conditions

Temperature: 120 °C

Procedure

Into a round bottom flask was added 5-(8-amino-3-cyclobutylimidazo[1,5-a]pyrazin-1-yl)-2-fluorobenzonitrile (30 mg, 0.0001 mol), phenol (0.023 g, 0.00024 mol), potassium carbonate (0.040 g, 0.00029 mol), DMF (0.8 mL, 0.01 mol) and the reaction mixture was heated at 120° C. for 4 h. Purification by Gilson HPLC afforded 11.4 mg of the title compound as a white solid. 1H NMR (400 MHz, CDCl3): δ=1.98-2.11 (m, 1H), 2.12-2.26 (m, 1H), 2.44-2.55 (m, 2H), 2.55-2.67 (m, 2H), 3.82 (dq, J=8.72, 8.55 Hz, 1H), 5.04 (br. s., 2H), 6.98 (d, J=8.84 Hz, 1H), 7.09 (d, J=5.05 Hz, 1H), 7.12-7.17 (m, 3H), 7.26-7.29 (m, 1H), 7.40-7.48 (m, 2H), 7.79 (dd, J=8.59, 2.27 Hz, 1H), 8.02 (d, J=2.02 Hz, 1H). MS (ES+): m/z 381.94 (100)[MH+]. HPLC: tR=2.53 min (Open Lynx, polar—5 min).

Workup

customPurification by Gilson HPLC

Sources & evidence

ORD record: ord-d0ad764770ef4e2d8363ebd999075adb
Source dataset: uspto-grants-2013_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08481733B2

Reaction notes

Loading…