HCID 67356521, compound → HCID 59352654, compound

HRID 1965587Notes

Reaction equation

HRID 1965587 reaction equation
C([O:8][C:9]1[CH:10]=[CH:11][C:12]([CH2:15][N:16]2[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[C:18]3([C:36]4[C:27](=[CH:28][C:29]5[O:34][CH2:33][CH2:32][O:31][C:30]=5[C:35]=4[F:37])[O:26][CH2:25]3)[C:17]2=[O:38])=[N:13][CH:14]=1)C1C=CC=CC=1>[Pd].C(O)(=O)C.CO>[F:37][C:35]1[C:30]2[O:31][CH2:32][CH2:33][O:34][C:29]=2[CH:28]=[C:27]2[O:26][CH2:25][C:18]3([C:19]4[C:24](=[CH:23][CH:22]=[CH:21][CH:20]=4)[N:16]([CH2:15][C:12]4[CH:11]=[CH:10][C:9]([OH:8])=[CH:14][N:13]=4)[C:17]3=[O:38])[C:36]=12

Participants

5

Reactant 1

HCID 67356521HCID 67356521, compound

Product 1

HCID 59352654HCID 59352654, compoundYield 46%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidCatalystHCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

Following the procedure as described in EXAMPLE 5.25 and making non-critical variations using 5-(benzyloxy)-2-(chloromethyl)pyridine hydrochloride to replace 2-(bromomethyl)pyridine hydrobromide, 1′-{[5-(benzyloxy)pyridine-2-yl]methyl}-9-fluoro-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-2′(1′H)-one (59%) was obtained as a colorless solid: MS (ES+) m/z 511.0 (M+1). A mixture of the 1′-{[5-(benzyloxy)pyridine-2-yl]methyl}-9-fluoro-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-2′(1′H)-one from the last step, palladium on carbon (10% w/w, 0.2 g), methanol (50 mL) and acetic acid (1 drop) was hydrogenated at a pressure of 50 psi at ambient temperature for 5 h. The reaction mixture was filtered and the filtrate was concentrated in vacuo. The residue was purified by column chromatography and eluted with a 0% to 70% gradient of ethyl acetate in dichloromethane to afford 9-fluoro-1′-[(5-hydroxypyridin-2-yl)methyl]-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-2′(1′H)-one (0.37 g, 46%) as an off-white solid: 1H NMR (300 MHz, DMSO-d6) δ9.88 (s, 1H), 8.00 (d, J=2.6 Hz, 1H), 7.25-7.09 (m, 4H), 7.01-6.87 (m, 2H), 6.12 (d, J=1.8 Hz, 1H), 4.88 (ABq, 2H), 4.82 (ABq, 2H), 4.29-4.09 (m, 4H); 13C NMR (75 MHz, DMSO-d6) δ176.0, 152.8, 145.2, 142.6, 141.5, 141.4, 138.7, 138.0, 137.1, 134.8, 133.4, 133.2, 131.0, 128.8, 123.5, 123.0, 122.8, 122.4, 122.2, 109.5, 106.0, 80.2, 64.3, 63.6, 57.5, 44.2; MS (ES+) m/z 421.1 (M+1).

Workup

  1. filtrationThe reaction mixture was filtered
  2. concentrationthe filtrate was concentrated in vacuo
  3. customThe residue was purified by column chromatography
  4. washeluted with a 0% to 70% gradient of ethyl acetate in dichloromethane

Sources & evidence

ORD record
ord-5374da3fbdd24eb3a6a0baa26f2bcdb1
Source dataset
uspto-grants-2013_04
Patent number
US08415370B2

Reaction notes

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