Hydrochloric Acid → HCID 51347040, compound

HRID 924907Notes

Reaction equation

[CH2:1]([O:3][C:4]1[CH:13]=[C:12]([CH:14]=O)[CH:11]=[C:10]([OH:16])[C:5]=1[C:6]([O:8]C)=[O:7])[CH3:2].[C:17]1([C:23](=O)[CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.[NH2:32][C:33]([NH2:35])=[O:34].Cl>CCO>[CH2:1]([O:3][C:4]1[CH:13]=[C:12]([CH:14]2[C:24]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)=[C:23]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[NH:35][C:33](=[O:34])[NH:32]2)[CH:11]=[C:10]([OH:16])[C:5]=1[C:6]([OH:8])=[O:7])[CH3:2]

Participants

Conditions

Temperature: 40 °C

Procedure

A mixture of methyl 2-ethoxy-4-formyl-6-hydroxybenzoate (Intermediate 85) (150 mg, 0.67 mmol), 1,2-diphenylethanone (137 mg, 0.70 mmol), urea (120 mg, 2.0 mmol) and conc. HCl (0.5 mL) in EtOH (5 mL) was refluxed under N2 overnight. The mixture was concentrated under reduced pressure. The residue was taken up in MeOH (10 mL) and aq. NaOH (2 M, 10 mL) and was stirred at 40° C. under N2 for 5 hours. The resulting mixture was cooled to room temperature, and then acidified with aqueous HCl (2 M, 12 mL), followed by a standard aqueous/EtOAc workup and purification by prep-HPLC (0.1% TFA as additive) to give Compound 161 (38 mg, 2-step yield 13%). 1H NMR (CD3OD 400 MHz): δ 7.25-7.20 (m, 5H), 7.08-7.00 (m, 3H), 6.89-6.84 (m, 2H), 6.62 (d, J=1.6 Hz, 1H), 6.47 (d, J=1.6 Hz, 1H), 5.24 (s, 1H), 4.17-4.04 (m, 2H), 1.37 (t, J=7.2 Hz, 3H). MS (ESI): m/z 431.5 [M+1]+.

Workup

temperaturewas refluxed under N2 overnight
concentrationThe mixture was concentrated under reduced pressure
temperatureThe resulting mixture was cooled to room temperature
customEtOAc workup and purification by prep-HPLC (0.1% TFA as additive)

Sources & evidence

ORD record: ord-5487312f89a04fde8f2b9d13745d80e9
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09283229B2

Reaction notes

Loading…