Trifluoroacetic acid → HCID 58465939, compound

HRID 455657Notes

Reaction equation

HRID 455657 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:50])=[CH:24][C:25]([C:44]4[CH2:45][CH2:46][O:47][CH2:48][CH:49]=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.C(Cl)Cl.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:47]1[CH2:48][CH:49]=[C:44]([C:25]2[CH:24]=[C:23]([F:50])[C:22]3[O:21][C:20]4[C:29](=[CH:30][C:17]([C:7]5[C:2]([F:1])=[N:3][CH:4]=[CH:5][CH:6]=5)=[CH:18][CH:19]=4)[C@:28]4([N:35]=[C:34]([NH2:36])[CH2:33][O:32][CH2:31]4)[C:27]=3[CH:26]=2)[CH2:45][CH2:46]1

Participants

8

Reactant 4

HCID 6422Trifluoroacetic acidHCID 10340Sodium CarbonateHCID 27832702-Fluoropyridine-3-boronic acidHCID 86761969HCID 86761969, compound

Product 1

HCID 58465939HCID 58465939, compoundYield 57.8%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
85 °C

Procedure

In a microwave vial, 2-fluoropyridin-3-ylboronic acid (0.048 g, 0.338 mmol), (S)-5-(tert-butoxycarbonylamino)-2′-(3,6-dihydro-2H-pyran-4-yl)-4′-fluoro-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthene]-7′-yl trifluoromethanesulfonate (0.166 g, 0.270 mmol), and Pd(PPh3)4 (0.031 g, 0.027 mmol) were suspended in DMF (3 mL). Aqueous sodium carbonate (1 M, 0.810 mL, 0.810 mmol) was added. Argon was blown through the vessel, which was sealed and heated in an 85° C. oil bath for 2.5 h. The reaction was cooled and concentrated. The residue was taken up in 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 transferred to a microwave vial in DCM (3 mL), and TFA (0.520 mL, 6.75 mmol) was added. The vial was sealed and heated in a 65° C. oil bath for 1.5 h. The mixture was cooled and concentrated, and the residue was neutralized with 0.5 M aqueous Na2CO3 (15 mL) and the aqueous phase was extracted with 5% 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 (50 mL) using 8% MeOH-DCM to afford 72 mg of (S)-2′-(3,6-dihydro-2H-pyran-4-yl)-4′-fluoro-7′-(2-fluoropyridin-3-yl)-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-5-amine. m/z=462.0[M+H]+.

Workup

  1. customwas sealed
  2. temperatureThe reaction was cooled
  3. concentrationconcentrated
  4. extractionthe aqueous phase was extracted with 3% MeOH-DCM (3×25 mL)
  5. washwashed with dilute brine (7 mL)
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated
  8. additionwas added
  9. customThe vial was sealed
  10. temperatureheated in a 65° C. oil bath for 1.5 h
  11. temperatureThe mixture was cooled
  12. concentrationconcentrated
  13. extractionthe aqueous phase was extracted with 5% MeOH-DCM (3×25 mL)
  14. washwashed with dilute brine (7 mL)
  15. dry with materialdried over sodium sulfate
  16. concentrationconcentrated
  17. customThe residue was purified through silica gel (50 mL)

Sources & evidence

ORD record
ord-52b68f6795ac4f2b89508aa7c07609e4
Source dataset
uspto-grants-2013_07
Patent number
US08497264B2

Reaction notes

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