Dimethylformamide → (S)-4'-fluoro-7'-(2-fluoropyridin-3-yl)-2'-morpholino-5H-spiro[oxazole-4,9'-xanthen]-2-amine

HRID 335930Notes

Reaction equation

HRID 335930 reaction equation
FC(F)(F)S(O[C:7]1[CH:20]=[C:19]2[C:10]([O:11][C:12]3[C:13]([F:32])=[CH:14][C:15]([N:26]4[CH2:31][CH2:30][O:29][CH2:28][CH2:27]4)=[CH:16][C:17]=3[C@@:18]32[CH2:24][O:23][C:22]([NH2:25])=[N:21]3)=[CH:9][CH:8]=1)(=O)=O.[F:35][C:36]1[C:41](B(O)O)=[CH:40][CH:39]=[CH:38][N:37]=1.CN(C=O)C.C(=O)([O-])[O-].[Na+].[Na+]>C(OCC)(=O)C.O.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.C(Cl)Cl>[F:32][C:13]1[C:12]2[O:11][C:10]3[C:19](=[CH:20][C:7]([C:41]4[C:36]([F:35])=[N:37][CH:38]=[CH:39][CH:40]=4)=[CH:8][CH:9]=3)[C@@:18]3([CH2:24][O:23][C:22]([NH2:25])=[N:21]3)[C:17]=2[CH:16]=[C:15]([N:26]2[CH2:31][CH2:30][O:29][CH2:28][CH2:27]2)[CH:14]=1

Participants

9

Reactant 4

HCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 27832702-Fluoropyridine-3-boronic acidHCID 86658488(S)-2-amino-4'-fluoro-2'-morpholino-5H-spiro[oxazole-4,9'-xanthene]-7'-yl trifluoromethanesulfonate

Product 1

HCID 53465003(S)-4'-fluoro-7'-(2-fluoropyridin-3-yl)-2'-morpholino-5H-spiro[oxazole-4,9'-xanthen]-2-amine

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
85 °C

Procedure

A resealable vial was charged with (S)-2-amino-4′-fluoro-2′-morpholino-5H-spiro[oxazole-4,9′-xanthene]-7′-yl trifluoromethanesulfonate (125 mg, 0.248 mmol; prepared by steps analogous to those described in Method BB40 and Example 2), tetrakis(triphenylphosphine)palladium(0) (28.7 mg, 0.025 mmol), 2-fluoropyridin-3-ylboronic acid (56.0 mg, 0.397 mmol), DMF (1.2 mL) and 2 M aqueous sodium carbonate (372 μL, 0.745 mmol). The vial was sealed and the mixture was stirred for 2 hr at 85° C. The mixture was cooled and diluted with ethyl acetate (6 mL) and water (2 ml). The organic layer was loaded onto 2 g SCX column and washed with EtOAc and MeOH/DCM 1:1. The material was recovered from the column with 2 M ammonia in MeOH, concentrated and purified by silica gel chromatography using 15-60% DCM/MeOH/NH4OH 90:10:1 in DCM to give a solid that was sonicated with 2 mL of DCM, then filtered and dried to afford (S)-4′-fluoro-7′-(2-fluoropyridin-3-yl)-2′-morpholino-5H-spiro[oxazole-4,9′-xanthen]-2-amine MS m/z=451.0 [M+H]+. Chemical Formula: C24H20F2N4O3. Exact Mass: 450.15.

Workup

  1. customprepared by steps analogous to
  2. customThe vial was sealed
  3. temperatureThe mixture was cooled
  4. washwashed with EtOAc and MeOH/DCM 1:1
  5. customThe material was recovered from the column with 2 M ammonia in MeOH
  6. concentrationconcentrated
  7. custompurified by silica gel chromatography
  8. customto give a solid
  9. filtrationfiltered
  10. customdried

Sources & evidence

ORD record
ord-38ad7daf5b654c25808b87178e67930a
Source dataset
uspto-grants-2014_11
Patent number
US08883782B2

Reaction notes

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