Sodium Carbonate → HCID 58465914, compound

HRID 455711Notes

Reaction equation

HRID 455711 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3](B(O)O)[CH:2]=1.FC(F)(F)S(O[C:16]1[CH:29]=[C:28]2[C:19]([O:20][C:21]3[C:22]([F:42])=[CH:23][C:24]([C:36]4[CH2:37][O:38][CH2:39][CH2:40][CH:41]=4)=[CH:25][C:26]=3[C@:27]32[N:34]=[C:33]([NH2:35])[CH2:32][O:31][CH2:30]3)=[CH:18][CH:17]=1)(=O)=O.C(=O)([O-])[O-].[Na+].[Na+]>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:38]1[CH2:39][CH2:40][CH:41]=[C:36]([C:24]2[CH:23]=[C:22]([F:42])[C:21]3[O:20][C:19]4[C:28](=[CH:29][C:16]([C:3]5[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=5)=[CH:17][CH:18]=4)[C@:27]4([N:34]=[C:33]([NH2:35])[CH2:32][O:31][CH2:30]4)[C:26]=3[CH:25]=2)[CH2:37]1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 27343783-Pyridinylboronic acidHCID 86658390HCID 86658390, compound

Product 1

HCID 58465914HCID 58465914, compoundYield 57.7%

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
85 °C

Procedure

In a microwave vial, the pyridin-3-ylboronic acid (0.061 g, 0.495 mmol), (S)-5-amino-2′-(5,6-dihydro-2H-pyran-3-yl)-4′-fluoro-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthene]-7′-yl trifluoromethanesulfonate (0.196 g, 0.381 mmol), and Pd(PPh3)4 (0.044 g, 0.038 mmol) were suspended in dmf (4.1 mL). Aqueous sodium carbonate (1.0 M, 1.143 mL, 1.143 mmol) was added. Argon was blown through the vessel, which was sealed and heated in an 85° C. oil bath (11:40). After 1.5 h the reaction was concentrated. The residue was taken up in EtOAc (100 mL) and the organic layer was extracted with water (15 mL), brine (, then was dried over sodium sulfate and concentrated. The residue was purified by chromatography (7.5% MeOH/DCM) to afford (S)-2′-(5,6-dihydro-2H-pyran-3-yl)-4′-fluoro-7′-(pyridin-3-yl)-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-5-amine (99 mg, 0.22 mmol). MS (m/z) 444 (M+H)+. 1H NMR (400 MHz, CDCl3) δ ppm; 8.85 (s, 1H), 8.57 (d, 1H, J=4.5 Hz), 7.86 (d, 1H, J=8.0 Hz), 7.50 (m, 2H), 7.36 (m, 2H), 7.08 (dd, 1H, J=11.7, 2.0 Hz), 6.99 (s, 1H), 6.17 (s, 1H), 4.46 (m, 2H), 4.33 (s, 2H), 3.85 (t, 2H, J=5.7 Hz), 3.57 (m, 2H), 2.33 (m, 2H).

Workup

  1. customwas sealed
  2. concentrationAfter 1.5 h the reaction was concentrated
  3. extractionthe organic layer was extracted with water (15 mL), brine (,
  4. dry with materialthen was dried over sodium sulfate
  5. concentrationconcentrated
  6. customThe residue was purified by chromatography (7.5% MeOH/DCM)

Sources & evidence

ORD record
ord-42792fa1995f4785a9b06ede4bae6d33
Source dataset
uspto-grants-2013_07
Patent number
US08497264B2

Reaction notes

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