Trifluoroacetic acid → HCID 58465897, compound

HRID 455719Notes

Reaction equation

HRID 455719 reaction equation
[C:1]([C:4]1[CH:5]=[C:6](B(OC(C)C)OC(C)C)[CH:7]=[N:8][CH:9]=1)#[C:2][CH3:3].FC(F)(F)S(O[C:25]1[CH:38]=[C:37]2[C:28]([O:29][C:30]3[C:31]([F:58])=[CH:32][C:33]([C:52]4[CH2:53][O:54][CH2:55][CH2:56][CH:57]=4)=[CH:34][C:35]=3[C@:36]32[N:43]=[C:42]([NH:44]C(OC(C)(C)C)=O)[CH2:41][O:40][CH2:39]3)=[CH:27][CH:26]=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:54]1[CH2:55][CH2:56][CH:57]=[C:52]([C:33]2[CH:32]=[C:31]([F:58])[C:30]3[O:29][C:28]4[C:37](=[CH:38][C:25]([C:6]5[CH:7]=[N:8][CH:9]=[C:4]([C:1]#[C:2][CH3:3])[CH:5]=5)=[CH:26][CH:27]=4)[C@:36]4([N:43]=[C:42]([NH2:44])[CH2:41][O:40][CH2:39]4)[C:35]=3[CH:34]=2)[CH2:53]1

Participants

8

Reactant 4

HCID 6422Trifluoroacetic acidHCID 10340Sodium CarbonateHCID 67387201HCID 67387201, compoundHCID 86658392HCID 86658392, compound

Product 1

HCID 58465897HCID 58465897, compoundYield 57.2%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
85 °C

Procedure

In a microwave vial, diisopropyl 5-(prop-1-ynyl)pyridin-3-ylboronate (0.109 g, 0.443 mmol), (S)-5-(tert-butoxycarbonylamino)-2′-(5,6-dihydro-2H-pyran-3-yl)-4′-fluoro-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthene]-7′-yl trifluoromethanesulfonate (0.218 g, 0.355 mmol), and Pd(PPh3)4 (0.041 g, 0.035 mmol) were taken up in DMF (3.7 mL). Aqueous sodium carbonate (1.0 M, 1.064 mL, 1.064 mmol) was added. Argon gas was blown through the vessel, which was sealed and heated in an 85° C. oil bath for 1.5 h. The reaction was concentrated. The residue was taken up in water (10 mL) and the aqueous phase was extracted with 5% MeOH/DCM (3×20 mL). The organics were combined, washed with dilute brine (5 mL), dried over sodium sulfate and concentrated. The residue was transferred to a microwave vial in DCM (2 mL), and TFA (0.683 mL, 8.87 mmol) was added. The vessel was sealed and heated in a 50° C. oil bath for 1.5 h. The reaction was concentrated, and the residue was neutralized with 0.5 M aqueous Na2CO3 (15 mL). The aqueous phase was extracted with 5% MeOH/DCM (3×20 mL). The organics were combined, washed with dilute brine (6 mL), dried over sodium sulfate and concentrated. The residue was purified by chromatography (7% MeOH/DCM) to afford (S)-2′-(5,6-dihydro-2H-pyran-3-yl)-4′-fluoro-7′-(5-(prop-1-ynyl)pyridin-3-yl)-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-5-amine (98 mg, 0.203 mmol).

Workup

  1. customwas sealed
  2. concentrationThe reaction was concentrated
  3. extractionthe aqueous phase was extracted with 5% MeOH/DCM (3×20 mL)
  4. washwashed with dilute brine (5 mL)
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. additionwas added
  8. customThe vessel was sealed
  9. temperatureheated in a 50° C. oil bath for 1.5 h
  10. concentrationThe reaction was concentrated
  11. extractionThe aqueous phase was extracted with 5% MeOH/DCM (3×20 mL)
  12. washwashed with dilute brine (6 mL)
  13. dry with materialdried over sodium sulfate
  14. concentrationconcentrated
  15. customThe residue was purified by chromatography (7% MeOH/DCM)

Sources & evidence

ORD record
ord-a8066c3e0e7947329d383a1143d6533a
Source dataset
uspto-grants-2013_07
Patent number
US08497264B2

Reaction notes

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