Hydrochloric Acid → HCID 51347043, compound

HRID 924911Notes

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-d896f1dfe474445580ddefa7f3a4cc05
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09283229B2

Reaction notes

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