Hydrochloric Acid → HCID 89784358, compound

HRID 1056095Notes

Reaction equation

HRID 1056095 reaction equation
[CH3:1][N:2]1[C:11](=[O:12])[C:10]2[C:5](=[C:6]([C:13]3[NH:21][C:20]4[CH2:19][CH2:18][NH:17][C:16](=[O:22])[C:15]=4[CH:14]=3)[CH:7]=[CH:8][CH:9]=2)[N:4]=[C:3]1SC.[NH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.Cl>CCOCC>[CH3:1][N:2]1[C:11](=[O:12])[C:10]2[C:5](=[C:6]([C:13]3[NH:21][C:20]4[CH2:19][CH2:18][NH:17][C:16](=[O:22])[C:15]=4[CH:14]=3)[CH:7]=[CH:8][CH:9]=2)[N:4]=[C:3]1[NH:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 6115AnilineHCID 89784543HCID 89784543, compound

Product 1

HCID 89784358HCID 89784358, compoundYield 4.2%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
150 °C

Procedure

A suspension of 3-methyl-2-(methylthio)-8-(4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)quinazolin-4(3H)-one (34.0 mg, 0.100 mmol), aniline (0.5 mL, 5.49 mmol), and HCl (conc.) (20 μl, 0.240 mmol) was heated by microwave in a sealed flask at 150° C. for 10 min. The mixture was diluted with Et2O (5 mL) and the precipitated solid was collected by vacuum filtration, washed with Et2O (5 mL), and dried in vacuo. Purification of the residue by revered-phase HPLC (Phenomenex Gemini C18 column (150×30 mm, 10 μm), 35 mL/min, 5-100% ACN/H2O+0.1% TFA) followed by supercritical-fluid chromatography (Chiralcel OD-H (250×21 mm, 5 μm), 50% liquid CO2/50% MeOH, 55 mL/min) afforded 3-methyl-8-(4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)-2-(phenylamino)quinazolin-4(3H)-one (1.6 mg, 4.15 μmol) as a white solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 8.98-9.15 (1H, m), 7.95-8.04 (1H, m), 7.81 (1H, d, J=7.6 Hz), 7.41-7.53 (5H, m), 7.23-7.33 (1H, m), 7.08-7.18 (1H, m), 6.89 (1H, s), 6.82 (1H, s), 3.61 (3H, s), 3.28 (2H, obsc. m), 2.33 (2H, m). m/z (ESI, +ve) 386.1 (M+H)+.

Workup

  1. filtrationthe precipitated solid was collected by vacuum filtration
  2. washwashed with Et2O (5 mL)
  3. customdried in vacuo
  4. customPurification of the residue by revered-phase HPLC (Phenomenex Gemini C18 column (150×30 mm, 10 μm), 35 mL/min, 5-100% ACN/H2O+0.1% TFA)

Sources & evidence

ORD record
ord-06f5ba93a6e640c4b470ebdf731164eb
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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