Reaction equation
[C:1]([C@@:3]1([F:25])[C@H:7]([OH:8])[CH2:6][O:5][C@H:4]1[N:9]1[CH:17]=[N:16][C:15]2[C:14](=[O:18])[NH:13][C:12]([NH:19]C(=O)C(C)C)=[N:11][C:10]1=2)#[CH:2]>N.C(OCC)(=O)C>[C:1]([C@@:3]1([F:25])[C@H:7]([OH:8])[CH2:6][O:5][C@H:4]1[N:9]1[CH:17]=[N:16][C:15]2[C:14](=[O:18])[NH:13][C:12]([NH2:19])=[N:11][C:10]1=2)#[CH:2]Participants
Procedure
Compound B4 (0.78 g, 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 D961 (Compound B5) (134 mg, 33%) as a yellow solid. NMR 1H (400 MHz, DMSO-d6): δ 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″).
Workup
- customThe reaction mixture was then evaporated to dryness under reduced pressure
- dissolutionThe residue was dissolved in water
- washwashed twice with ethyl acetate
- customThe aqueous layer was evaporated
- custompurified on reverse phase column chromatography (C18)
- washeluting with a gradient 2-15% of acetonitrile in water
- customThe residue obtained
- filtrationfiltered
- customdried
Sources & evidence
- ORD record
- ord-1d8810b0185f4d52a09e87be8008321e
- Source dataset
- uspto-grants-2016_02
- Patent number
- US09249173B2
Linked notes
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