2-(Tributylstannyl)pyrazine → (S)-3-(2-amino-5'-fluoro-2'-(pyrazin-2-yl)-5H-spiro[oxazole-4,9'-xanthene]-7'-yloxy)-2,2-dimethylpropanenitrile

HRID 335834Notes

Reaction equation

C([Sn](CCCC)(CCCC)[C:6]1[CH:11]=[N:10][CH:9]=[CH:8][N:7]=1)CCC.[NH2:20][C:21]1[O:22][CH2:23][C@:24]2([N:47]=1)[C:37]1[CH:36]=[C:35](Br)[CH:34]=[CH:33][C:32]=1[O:31][C:30]1[C:25]2=[CH:26][C:27]([O:40][CH2:41][C:42]([CH3:46])([CH3:45])[C:43]#[N:44])=[CH:28][C:29]=1[F:39]>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.CN(C=O)C>[NH2:20][C:21]1[O:22][CH2:23][C@:24]2([N:47]=1)[C:37]1[CH:36]=[C:35]([C:6]3[CH:11]=[N:10][CH:9]=[CH:8][N:7]=3)[CH:34]=[CH:33][C:32]=1[O:31][C:30]1[C:25]2=[CH:26][C:27]([O:40][CH2:41][C:42]([CH3:45])([CH3:46])[C:43]#[N:44])=[CH:28][C:29]=1[F:39]

Participants

Conditions

Temperature: 100 °C

Procedure

To a flask charged with Pd(PPh3)4 (8.82 mg, 0.034 mmol), 2-(tributylstannyl)pyrazine (248 mg, 0.672 mmol), and (S)-3-(2-amino-2′-bromo-5′-fluoro-5H-spiro[oxazole-4,9′-xanthene]-7′-yloxy)-2,2-dimethylpropanenitrile (150 mg, 0.336 mmol) was added 3 ml of DMF. The resulting mixture was heated in the microwave at 100° C. for one hour. The solution was concentrated in vacuo and the derived residue was purified by HPLC (gradient elution 10-90% MeCN/H2O, 0.1% TFA) to afford (S)-3-(2-amino-5′-fluoro-2′-(pyrazin-2-yl)-5H-spiro[oxazole-4,9′-xanthene]-7′-yloxy)-2,2-dimethylpropanenitrile as a white solid. MS m/z=446.0 [M+H].

Workup

concentrationThe solution was concentrated in vacuo
customthe derived residue was purified by HPLC (gradient elution 10-90% MeCN/H2O, 0.1% TFA)

Sources & evidence

ORD record: ord-0a8adcec9a754fb4ba245d87afcdc5ea
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08883782B2

Reaction notes

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