Trifluoroacetic acid → HCID 58465999, compound

HRID 455662Notes

Reaction equation

HRID 455662 reaction equation
[F:1][C:2]1[C:7](B(O)O)=[CH:6][CH:5]=[CH:4][N:3]=1.FC(F)(F)S(O[C:17]1[CH:30]=[C:29]2[C:20]([O:21][C:22]3[C:23]([F:51])=[CH:24][C:25]([C:44]#[C:45][C:46]4([CH3:50])[CH2:49][O:48][CH2:47]4)=[CH:26][C:27]=3[C@:28]32[N:35]=[C:34]([NH:36]C(OC(C)(C)C)=O)[CH2:33][O:32][CH2:31]3)=[CH:19][CH:18]=1)(=O)=O.C(=O)([O-])[O-].[Na+].[Na+].C(O)(C(F)(F)F)=O>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:51][C:23]1[C:22]2[O:21][C:20]3[C:29](=[CH:30][C:17]([C:7]4[C:2]([F:1])=[N:3][CH:4]=[CH:5][CH:6]=4)=[CH:18][CH:19]=3)[C@:28]3([N:35]=[C:34]([NH2:36])[CH2:33][O:32][CH2:31]3)[C:27]=2[CH:26]=[C:25]([C:44]#[C:45][C:46]2([CH3:50])[CH2:49][O:48][CH2:47]2)[CH:24]=1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 10340Sodium CarbonateHCID 27832702-Fluoropyridine-3-boronic acidHCID 86761972HCID 86761972, compound

Product 1

HCID 58465999HCID 58465999, compoundYield 15.5%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

In a microwave vial, 2-fluoropyridin-3-ylboronic acid (0.065 g, 0.459 mmol), Pd(PPh3)4 (0.042 g, 0.037 mmol) and (S)-5-(tert-butoxycarbonylamino)-4′-fluoro-2′-((3-methyloxetan-3-yl)ethynyl)-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthene]-7′-yl trifluoromethanesulfonate (0.230 g, 0.367 mmol) were taken up in DMF (3 mL). Aqueous sodium carbonate (1.0 M, 1.10 mL, 1.10 mmol) was added. Argon was blown through the vessel which was then sealed and heated in an 85° C. oil bath for 4 h. The reaction was cooled and concentrated, and the residue was diluted with water (15 mL) and the aqueous phase was extracted with 3% MeOH-DCM (3×25 mL). The organics were combined, washed with dilute brine (7 mL), dried over sodium sulfate and concentrated. The residue was purified through silica gel (33 mL) which had been deactivated with Et3N (3.3 mL), using 33% EtOAc in hexane. The resulting residue was transferred to a microwave vessel in DCM (3 mL), and TFA (0.283 mL, 3.67 mmol) was added. The vessel was sealed and heated in a 60° C. oil bath for 1.5 h. The reaction was cooled and concentrated, and the residue was neutralized with 0.5 M aqueous Na2CO3 (15 mL). The aqueous phase was extracted with 5% MeOH-DCM (3×25 mL). The organics were combined, washed with dilute brine (7 mL) and dried over sodium sulfate. The residue was purified through silica gel (33 mL) using 7.5% MeOH-DCM to afford 27 mg of (S)-4′-fluoro-7′-(2-fluoropyridin-3-yl)-2′-((3-methyloxetan-3-yl)ethynyl)-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-5-amine. m/z=474.0[M+H]+.

Workup

  1. customwas then sealed
  2. temperatureThe reaction was cooled
  3. concentrationconcentrated
  4. additionthe residue was diluted with water (15 mL)
  5. extractionthe aqueous phase was extracted with 3% MeOH-DCM (3×25 mL)
  6. washwashed with dilute brine (7 mL)
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated
  9. customThe residue was purified through silica gel (33 mL) which
  10. customThe resulting residue was transferred to a microwave vessel in DCM (3 mL)
  11. customThe vessel was sealed
  12. temperatureheated in a 60° C. oil bath for 1.5 h
  13. temperatureThe reaction was cooled
  14. concentrationconcentrated
  15. extractionThe aqueous phase was extracted with 5% MeOH-DCM (3×25 mL)
  16. washwashed with dilute brine (7 mL)
  17. dry with materialdried over sodium sulfate
  18. customThe residue was purified through silica gel (33 mL)

Sources & evidence

ORD record
ord-a9d94d49ec3d4c7d87bd139dad9b4941
Source dataset
uspto-grants-2013_07
Patent number
US08497264B2

Reaction notes

Loading…