HCID 136343924, compound → HCID 136195916, compound

HRID 1772293Notes

Reaction equation

HRID 1772293 reaction equation
C([NH:6][C:7]1[NH:8][C:9](=[O:27])[C:10]2[N:11]=[CH:12][N:13]([C@@H:16]3[O:21][C@H:20]([CH2:22][OH:23])[C@@H:18]([OH:19])[C@@:17]3([C:25]#[CH:26])[F:24])[C:14]=2[N:15]=1)(=O)C(C)C>N.C(OCC)(=O)C>[C:25]([C@@:17]1([F:24])[C@H:18]([OH:19])[C@@H:20]([CH2:22][OH:23])[O:21][C@H:16]1[N:13]1[CH:12]=[N:11][C:10]2[C:9](=[O:27])[NH:8][C:7]([NH2:6])=[N:15][C:14]1=2)#[CH:26]

Participants

4

Reactant 1

HCID 136343924HCID 136343924, compound

Product 1

HCID 136195916HCID 136195916, compoundYield 33%

Reagents, catalysts & solvents 2

HCID 222AmmoniaSolventHCID 8857Ethyl AcetateSolvent

Procedure

6b (1.33 mmol) was dissolved in saturated methanolic ammonia (62 mL) and stirred at room temperature for 20 h. The reaction mixture was then evaporated to dryness under reduced pressure. The residue was dissolved in water and washed twice with ethyl acetate. The aqueous layer was evaporated and purified on reverse phase column chromatography (C18) eluting with a gradient 2-15% of acetonitrile in water. The residue obtained was then dissolved in hot ethyl acetate, filtered and dried to give the title compound (134 mg, 33%). Yellow solid. Molecular Formula C12H12FN5O4 1H NMR (DMSO-d6, 400 MHz) δ(ppm) 10.70 (1s, 1H, NH), 7.98 (s, 1H, H-8), 6.60 (1s, 2H, NH2), 6.21 (d, 1H, OH-3′, JOH-3′=7.6 Hz), 5.83 (d, 1H, H-1′, J1′-F=16.9 Hz), 5.29 (t, 1H, OH-5′, JOH-5′=5.2 Hz), 4.50 (td, 1H, H-3′, J3′-F=22.8 Hz, J3′-4′=9.2 Hz), 3.93-3.81 (m, 3H, H-4′, H-5′ and ethynyl), 3.70 (m, 1H, H-5″). BC NMR (DMSO-d6, 100 MHz) δ(ppm) 157.2 (C-6), 154.3 (C-2), 151.05 (C-4), 135.1 (C-8), 116.7 (C-5), 96.4 (d, C-2′, 1JC—F=182.1 Hz), 87.4 (d, C-1′, 2JC—F=39.2 Hz), 83.1 (d, CCH, JC—F=9.1 Hz), 82.4 (C-4′), 76.2 (d, CCH, 2JC—F=31.2 Hz), 73.2 (d, C-3′, 2JC—F=20.1 Hz), 59.5 (C-5′). 19F NMR (DMSO-d6, 235 MHz) δ(ppm) −158.5 (m). LC/MS (A): (M+H+) 310.1 (5.55 min). LRFAB-MS (GT): 619 (2M+H)+, 310 (M+H)+, 152 (B+H)+, 617 (2M−H)−, 308 (M−H)−. UV λmax 253 nm

Workup

  1. customThe reaction mixture was then evaporated to dryness under reduced pressure
  2. dissolutionThe residue was dissolved in water
  3. washwashed twice with ethyl acetate
  4. customThe aqueous layer was evaporated
  5. custompurified on reverse phase column chromatography (C18)
  6. washeluting with a gradient 2-15% of acetonitrile in water
  7. customThe residue obtained
  8. filtrationfiltered
  9. customdried

Sources & evidence

ORD record
ord-de5e23e780b94f1895bbe37fc91f4508
Source dataset
uspto-grants-2016_02
Patent number
US09249173B2

Reaction notes

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