Sodium Carbonate → (4S)-2'-(3,6-dihydro-2H-pyran-5-yl)-4'-fluoro-7'-(2-fluoro-3-pyridinyl)spiro[5H-1,3-oxazole-4,9'-xanthene]-2-amine

HRID 335921Notes

Reaction equation

HRID 335921 reaction equation
C(=O)([O-])[O-].[Na+].[Na+].FC(F)(F)S(O[C:13]1[CH:26]=[C:25]2[C:16]([O:17][C:18]3[CH:19]=[CH:20][C:21]([C:32]4[C:33]([F:38])=[N:34][CH:35]=[CH:36][CH:37]=4)=[CH:22][C:23]=3[C@:24]32[CH2:30][O:29][C:28]([NH2:31])=[N:27]3)=[C:15]([F:39])[CH:14]=1)(=O)=O.[O:42]1[CH2:47][CH2:46][CH:45]=[C:44](B2OC(C)(C)C(C)(C)O2)[CH2:43]1>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>[O:42]1[CH2:47][CH2:46][CH:45]=[C:44]([C:13]2[CH:14]=[C:15]([F:39])[C:16]3[O:17][C:18]4[C:23](=[CH:22][C:21]([C:32]5[C:33]([F:38])=[N:34][CH:35]=[CH:36][CH:37]=5)=[CH:20][CH:19]=4)[C@@:24]4([CH2:30][O:29][C:28]([NH2:31])=[N:27]4)[C:25]=3[CH:26]=2)[CH2:43]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 158366332-(5,6-dihydro-2H-pyran-3-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 86640722(S)-2-amino-5'-fluoro-2'-(2-fluoropyridin-3-yl)-5H-spiro[oxazole-4,9'-xanthene]-7'-yl trifluoromethanesulfonate

Product 1

HCID 53464942(4S)-2'-(3,6-dihydro-2H-pyran-5-yl)-4'-fluoro-7'-(2-fluoro-3-pyridinyl)spiro[5H-1,3-oxazole-4,9'-xanthene]-2-amine

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

Sodium carbonate (saturated) (1 ml), Pd(PPh3)4 (53.5 mg, 0.046 mmol), (S)-2-amino-5′-fluoro-2′-(2-fluoropyridin-3-yl)-5H-spiro[oxazole-4,9′-xanthene]-7′-yl trifluoromethanesulfonate (475 mg, 0.925 mmol; prepared from the alcohol by steps analogous to those described in Method BB40 and Example 2), and 2-(5,6-dihydro-2H-pyran-3-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (389 mg, 1.850 mmol) were combined in DMF (5 ml). The solution was heated at 85° C. for three hours before being cooled to rt. The solution was concentrated and the derived residue was purified via silica gel column chromatography (RediSep 40 g column) using 20-70% 90/10/1 (CH2Cl2/MeOH/ammonia) in CH2Cl2 to afford (S)-2′-(5,6-dihydro-2H-pyran-3-yl)-4′-fluoro-7′-(2-fluoropyridin-3-yl)-5H-spiro[oxazole-4,9′-xanthen]-2-amine as a white solid. MS m/z=448.0 [M+H]+. Chemical Formula: C25H19F2N3O3. Exact Mass: 447.14. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.18-2.36 (m, 2 H) 3.75 (t, J=5.5 Hz, 2 H) 4.24 (m, 2 H) 4.30-4.48 (m, 2 H) 6.22-6.36 (m, 1 H) 6.52 (s, 2 H) 7.07-7.15 (m, 1 H) 7.38 (m, J=8.5 Hz, 2 H) 7.50 (ddd, J=7.4, 4.9, 1.9 Hz, 1 H) 7.53-7.66 (m, 2 H) 8.12 (ddd, J=10.4, 7.5, 1.9 Hz, 1 H) 8.20-8.30 (m, 1 H)

Workup

  1. temperaturebefore being cooled to rt
  2. concentrationThe solution was concentrated
  3. customthe derived residue was purified via silica gel column chromatography (RediSep 40 g column)

Sources & evidence

ORD record
ord-30053e92959e422bacaec7712d4e7582
Source dataset
uspto-grants-2014_11
Patent number
US08883782B2

Reaction notes

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