Hydrochloric Acid → HCID 51347043, compound

HRID 2178006Notes

Reaction equation

[CH:1]([C:3]1[CH:12]=[C:11]([O:13][CH3:14])[C:6]([C:7]([O:9]C)=[O:8])=[C:5]([OH:15])[CH:4]=1)=O.[C:16]1([C:22](=O)[CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.[NH2:31][C:32]([NH2:34])=[O:33].Cl>CCO>[OH:15][C:5]1[CH:4]=[C:3]([CH:1]2[C:23]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[C:22]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[NH:34][C:32](=[O:33])[NH:31]2)[CH:12]=[C:11]([O:13][CH3:14])[C:6]=1[C:7]([OH:9])=[O:8]

Participants

Conditions

Temperature: 50 °C

Procedure

A mixture of methyl 4-formyl-2-hydroxy-6-methoxybenzoate (Intermediate 87) (150 mg, 0.76 mmol), 1,2-diphenylethanone (160 mg, 0.76 mmol), urea (150 mg, 2.5 mmol) and conc. HCl (0.5 mL) in EtOH (5 mL) was refluxed under N2 overnight. The mixture was concentrated in vacuo. The residue was taken up in MeOH (10 mL) and aq. NaOH (2 M, 10 mL) and was stirred at 50° C. under N2 for 5 hours. The resulting mixture was cooled, and then acidified with aqueous HCl (2 M, 12 mL) to pH=3 followed by a standard aqueous/EtOAc workup and purification by prep-HPLC (0.1% TFA as additive) to give Compound 165 (31 mg, 2-step yield 10%). 1H NMR (CD3OD 400 MHz): δ 7.30-7.20 (m, 5H), 7.12-7.06 (m, 3H), 6.94-6.88 (m, 2H), 6.67 (d, J=1.6 Hz, 1H), 6.50 (d, J=1.6 Hz, 1H), 5.29 (s, 1H), 3.85 (s, 3H). MS (ESI): m/z 417.4 [M+1]+.

Workup

temperaturewas refluxed under N2 overnight
concentrationThe mixture was concentrated in vacuo
temperatureThe resulting mixture was cooled
customEtOAc workup and purification by prep-HPLC (0.1% TFA as additive)

Sources & evidence

ORD record: ord-ce8add2fddd045d2b334e5d1d1a49f51
Source dataset: uspto-grants-2015_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09067893B2

Reaction notes

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