Phenol → HCID 136500832, compound

HRID 1055853Notes

Reaction equation

[H-].[Na+].[C:3]1([OH:9])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.Cl.Cl[C:12]1[CH:21]=[CH:20][C:19]2[C:14](=[C:15]([C:22]3[NH:31][C:25]4[N:26]=[CH:27][NH:28][C:29](=[O:30])[C:24]=4[CH:23]=3)[CH:16]=[CH:17][CH:18]=2)[N:13]=1.C(O)(C(F)(F)F)=O>CN(C=O)C.CS(C)=O>[O:9]([C:12]1[CH:21]=[CH:20][C:19]2[C:14](=[C:15]([C:22]3[NH:31][C:25]4[N:26]=[CH:27][NH:28][C:29](=[O:30])[C:24]=4[CH:23]=3)[CH:16]=[CH:17][CH:18]=2)[N:13]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1

Participants

Conditions

Temperature: 70 °C

Procedure

NaH (60% in mineral oil; 0.063 g, 1.576 mmol) was suspended in 1 mL DMF and phenol (0.148 g, 1.576 mmol) was added. After 10 min, 6-(2-chloroquinolin-8-yl)-3H-pyrrolo[2,3-d]pyrimidin-4(7H)-one hydrochloride (Example 19b; 0.075 g, 0.225 mmol) was added, and the reaction was sealed and heated at 70° C. for 2 h, then at 90° C. for 1 h. The reaction was treated with TFA (0.121 ml, 1.576 mmol) and 1 mL DMSO, filtered, and purified by rpHPLC (Phenomenex Gemini 150×30 mm C18 column, 20-100% ACN/H2O with 0.1% TFA); product-containing fractions were concentrated in vacuo to give 6-(2-phenoxyquinolin-8-yl)-3H-pyrrolo[2,3-d]pyrimidin-4(7H)-one (0.022 g, 0.062 mmol, 28% yield) as a yellow solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 11.72 (1H, br. s), 11.64 (1H, br. s), 8.50 (1H, d, J=8.8 Hz), 8.22 (1H, dd, J=7.5, 1.5 Hz), 7.90 (1H, dd, J=8.0, 1.4 Hz), 7.81 (1H, d, J=3.7 Hz), 7.49-7.58 (3H, m), 7.30-7.42 (4H, m), 7.13 (1H, d, J=2.3 Hz). m/z (ESI, +ve) 355.0 (M+H)+.

Workup

customthe reaction was sealed
waitat 90° C. for 1 h
filtrationfiltered
custompurified by rpHPLC (Phenomenex Gemini 150×30 mm C18 column, 20-100% ACN/H2O with 0.1% TFA)
concentrationproduct-containing fractions were concentrated in vacuo

Sources & evidence

ORD record: ord-15c580c00b7e4d6080dd18828b2b8f3d
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09394297B2

Reaction notes

Loading…