Dimethylformamide → (S)-2-amino-4'-fluoro-7'-(pyrimidin-5-yl)-5H-spiro[oxazole-4,9'-xanthen]-2'-ol

HRID 1970319Notes

Reaction equation

[NH2:1][C:2]1[O:3][CH2:4][C@@:5]2([N:22]=1)[C:18]1[CH:17]=[C:16]([OH:19])[CH:15]=[C:14]([F:20])[C:13]=1[O:12][C:11]1[C:6]2=[CH:7][C:8](Br)=[CH:9][CH:10]=1.[N:23]1[CH:28]=[C:27](B(O)O)[CH:26]=[N:25][CH:24]=1.CN(C=O)C.C(=O)([O-])[O-].[Na+].[Na+]>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.O>[NH2:1][C:2]1[O:3][CH2:4][C@@:5]2([N:22]=1)[C:18]1[CH:17]=[C:16]([OH:19])[CH:15]=[C:14]([F:20])[C:13]=1[O:12][C:11]1[C:6]2=[CH:7][C:8]([C:27]2[CH:28]=[N:23][CH:24]=[N:25][CH:26]=2)=[CH:9][CH:10]=1

Participants

Conditions

Temperature: 85 °C

Procedure

A 25 ml RBF was charged with (S)-2-amino-7′-bromo-4′-fluoro-5H-spiro[oxazole-4,9′-xanthen]-2′-ol (629 mg, 1.723 mmol), tetrakis(triphenylphosphine)palladium (199 mg, 0.172 mmol), and pyrimidin-5-ylboronic acid (320 mg, 2.58 mmol). DMF (8613 μL) and sodium carbonate (2M solution) (2584 μL, 5.17 mmol) were added and the mixture was stirred at 85° C. for 2.5 hrs. The mixture was cooled to RT, water (−5 ml) was added and stirring was continued for 10 min. The precipitate was filtered out, washed with water (3×5 mL), 1:1 i-PrOH/water to remove color and dried in vacuo to afford (S)-2-amino-4′-fluoro-7′-(pyrimidin-5-yl)-5H-spiro[oxazole-4,9′-xanthen]-2′-ol as yellow solid.

Workup

temperatureThe mixture was cooled to RT
stirringstirring
waitwas continued for 10 min
filtrationThe precipitate was filtered out
washwashed with water (3×5 mL), 1:1 i-PrOH/water
customto remove color
customdried in vacuo

Sources & evidence

ORD record: ord-e3c35f31f2ef4b469aed0839743fddc2
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08426447B2

Reaction notes

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