Water → 4-Amino-6'-cyclopropyl-3-fluoro-5-methoxy-[2,3'-bipyridine]-6-carboxylic acid

HRID 407261Notes

Reaction equation

HRID 407261 reaction equation
[NH2:1][C:2]1[C:7]([O:8][CH3:9])=[C:6]([C:10]([O:12]C)=[O:11])[N:5]=[C:4]([C:14]2[CH:15]=[N:16][C:17]([CH:20]3[CH2:22][CH2:21]3)=[CH:18][CH:19]=2)[C:3]=1[F:23].O.O.[OH-].[Li+]>C1COCC1.CO>[NH2:1][C:2]1[C:7]([O:8][CH3:9])=[C:6]([C:10]([OH:12])=[O:11])[N:5]=[C:4]([C:14]2[CH:15]=[N:16][C:17]([CH:20]3[CH2:21][CH2:22]3)=[CH:18][CH:19]=2)[C:3]=1[F:23]

Participants

6

Reactant 3

HCID 962WaterHCID 168937Lithium hydroxide, monohydrateHCID 71150560Methyl 4-amino-6'-cyclopropyl-3-fluoro-5-methoxy-[2,3'-bipyridine]-6-carboxylate

Product 1

HCID 711507314-Amino-6'-cyclopropyl-3-fluoro-5-methoxy-[2,3'-bipyridine]-6-carboxylic acidYield 52.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl 4-amino-6′-cyclopropyl-3-fluoro-5-methoxy-[2,3′-bipyridine]-6-carboxylate (100 mg, 0.315 mmol) in THF (1.00 mL), MeOH (1.000 mL), and Water (0.500 mL), lithium hydroxide hydrate (65 mg, 1.549 mmol) was added as a solid. The reaction was allowed to stir at room temperature for 18 hrs. The reaction solution was then concentrated under vacuum to dryness. The resulting solid was suspended in H2O and the pH was adjusted to 4.0, forming a ppt. The suspension was extracted with EtOAc (3×25 mL). The combined organic layers were dried over MgSO4, filtered and concentrated under vacuum to yield 4-amino-6′-cyclopropyl-3-fluoro-5-methoxy-[2,3′-bipyridine]-6-carboxylic acid (50.0 mg, 0.165 mmol, 52.3% yield). ESIMS for m/z 304 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ 0.92-1.06 (m, 4H), 2.17 (tt, J=7.8, 5.1 Hz, 1H), 3.78 (s, 3H), 6.49 (s, 2H), 7.42 (dd, J=8.3, 0.9 Hz, 1H), 8.05 (ddd, J=8.2, 2.2, 1.1 Hz, 1H), 8.81 (t, J=2.0 Hz, 1H), 13.03 (s, 1H). 19F NMR (376 MHz, DMSO-d6) δ −141.73.

Workup

  1. concentrationThe reaction solution was then concentrated under vacuum to dryness
  2. customforming a ppt
  3. extractionThe suspension was extracted with EtOAc (3×25 mL)
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-bd942cd74ab14f0495f6a4695321c6b7
Source dataset
uspto-grants-2014_06
Patent number
US08754229B2

Reaction notes

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