Sodium Carbonate → (S)-4'-fluoro-7'-(2-fluoropyridin-3-yl)-2'-(6-methylpyridazin-3-yl)-5H-spiro[oxazole-4,9'-xanthen]-2-amine

HRID 335891Notes

Reaction equation

C(=O)([O-])[O-].[Na+].[Na+].[F:7][C:8]1[C:21]2[O:20][C:19]3[C:14](=[CH:15][C:16]([C:22]4[C:23]([F:28])=[N:24][CH:25]=[CH:26][CH:27]=4)=[CH:17][CH:18]=3)[C@@:13]3([CH2:32][O:31][C:30]([NH2:33])=[N:29]3)[C:12]=2[CH:11]=[C:10](B2OC(C)(C)C(C)(C)O2)[CH:9]=1.Br[C:44]1[N:45]=[N:46][C:47]([CH3:50])=[CH:48][CH:49]=1>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:7][C:8]1[C:21]2[O:20][C:19]3[C:14](=[CH:15][C:16]([C:22]4[C:23]([F:28])=[N:24][CH:25]=[CH:26][CH:27]=4)=[CH:17][CH:18]=3)[C@@:13]3([CH2:32][O:31][C:30]([NH2:33])=[N:29]3)[C:12]=2[CH:11]=[C:10]([C:44]2[N:45]=[N:46][C:47]([CH3:50])=[CH:48][CH:49]=2)[CH:9]=1

Participants

Conditions

Temperature: 85 °C

Procedure

Sodium carbonate (saturated, 1 mL), Pd(PPh3)4 (23.52 mg, 0.020 mmol), (S)-4′-fluoro-7′-(2-fluoropyridin-3-yl)-2′-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5H-spiro[oxazole-4,9′-xanthen]-2-amine (200 mg, 0.407 mmol), and 3-bromo-6-methylpyridazine (141 mg, 0.814 mmol) were combined in DMF (5 mL). The solution was heated at 85° C. overnight. The solution was filtered through celite and the derived residue was purified via Gilson HPLC (gradient elution 25-65% MeCN/H2O, 0.1% TFA) to afford (S)-4′-fluoro-7′-(2-fluoropyridin-3-yl)-2′-(6-methylpyridazin-3-yl)-5H-spiro[oxazole-4,9′-xanthen]-2-amine as an off white solid. MS m/z=458.0 [M+H].

Workup

filtrationThe solution was filtered through celite
customthe derived residue was purified via Gilson HPLC (gradient elution 25-65% MeCN/H2O, 0.1% TFA)

Sources & evidence

ORD record: ord-b8643917816a4f93a630ebe78fcb4b20
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08883782B2

Reaction notes

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