Phenol → HCID 67815363, compound

HRID 2401383Notes

Reaction equation

Cl[C:2]1[C:3]2[C:23]([CH3:24])=[C:22]([CH3:25])[S:21][C:4]=2[C:5]2[C:19]([CH3:20])=[N:18][O:17][C:6]=2[C@H:7]([CH2:9][C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[N:8]=1.[C:26]1([OH:32])[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>N1C=CC=CC=1>[CH3:25][C:22]1[S:21][C:4]2[C:5]3[C:19]([CH3:20])=[N:18][O:17][C:6]=3[C@H:7]([CH2:9][C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[N:8]=[C:2]([O:32][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[C:3]=2[C:23]=1[CH3:24]

Participants

Conditions

Temperature: 130 °C

Procedure

A mixture of tert-butyl 2-((6S)-4-chloro-2,3,9-trimethyl-6H-isoxazolo[5,4-c]thieno[2,3-e]azepin-6-yl)acetate, a form of intermediate 18, prepared according to Example 14 (0.220 g, 0.58 mmol) and phenol (0.276 g, 2.90 mmol) in pyridine (1 mL) was heated at 130° C. for 1 h by MW. After the solvent was removed in vacuo, the residue was washed with 1 N NaOH, dried by anhydrous Na2SO4. The product was purified by Prep-TLC (PE:EA=4:1) to give tert-butyl 2-((6S)-2,3,9-trimethyl-4-phenoxy-6H-isoxazolo[5,4-c]thieno[2,3-e]azepin-6-yl)acetate (0.020 g, 7.9% yield) as a white solid. tert-butyl 2-((6S)-2,3,9-trimethyl-4-phenoxy-6H-isoxazolo[5,4-c]thieno[2,3-e]azepin-6-yl)acetate was converted to target compound 2-((6S)-2,3,9-trimethyl-4-phenoxy-6H-isoxazolo[5,4-c]thieno[2,3-e]azepin-6-yl)acetamide using Step L in Example 14. 1H NMR (300 MHz, CDCl3) δ 7.39-7.34 (m, 2H), 7.22-7.07 (m, 3H), 6.07 (s, 1H), 5.18 (s, 1H), 4.46 (q, J=4.5 Hz, 1H), 2.99-2.84 (m, 2H), 2.48 (s, 3H), 2.45 (s, 3H), 2.42 (s, 3H); LC/MS m/z 382 [M+H]+.

Workup

customAfter the solvent was removed in vacuo
washthe residue was washed with 1 N NaOH
dry with materialdried by anhydrous Na2SO4
customThe product was purified by Prep-TLC (PE:EA=4:1)

Sources & evidence

ORD record: ord-631d7ba0c7a14bdeae8d537fb3e79c4a
Source dataset: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08796261B2

Reaction notes

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