Methyl 3-fluoro-4-(2-(5-nitropyridin-2-ylamino)thiazol-5-ylthio)picolinate → Methyl 4-(2-(5-aminopyridin-2-ylamino)thiazol-5-ylthio)-3-fluoropicolinate

HRID 1685352Notes

Reaction equation

HRID 1685352 reaction equation
[F:1][C:2]1[C:3]([C:24]([O:26][CH3:27])=[O:25])=[N:4][CH:5]=[CH:6][C:7]=1[S:8][C:9]1[S:13][C:12]([NH:14][C:15]2[CH:20]=[CH:19][C:18]([N+:21]([O-])=O)=[CH:17][N:16]=2)=[N:11][CH:10]=1>C(O)(=O)C.C1COCC1.[Pt]>[NH2:21][C:18]1[CH:19]=[CH:20][C:15]([NH:14][C:12]2[S:13][C:9]([S:8][C:7]3[CH:6]=[CH:5][N:4]=[C:3]([C:24]([O:26][CH3:27])=[O:25])[C:2]=3[F:1])=[CH:10][N:11]=2)=[N:16][CH:17]=1

Participants

5

Reactant 1

HCID 59200453Methyl 3-fluoro-4-(2-(5-nitropyridin-2-ylamino)thiazol-5-ylthio)picolinate

Product 1

HCID 59200430Methyl 4-(2-(5-aminopyridin-2-ylamino)thiazol-5-ylthio)-3-fluoropicolinate

Reagents, catalysts & solvents 3

HCID 23939PlatinumCatalyst2×HCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolvent

Procedure

A stirring solution of methyl 3-fluoro-4-(2-(5-nitropyridin-2-ylamino)thiazol-5-ylthio)picolinate (1.77 g, 4.34 mmol), 10% Pt/C (366 mg) in acetic acid (5 mL) and THF (20 mL) was purged 4× with H2, then pressurized to 140 psi in a steel bomb reactor and stirred overnight. The reaction was depressurized, and LCMS showed intermediate nitroso as predominant product. Pt/C (270 mg) was added and the reaction repressurized to 140 psi and stirred overnight. The reaction was depressurized, LCMS showed complete reaction. The reaction was filtered through Celite, washed with THF and DCM, the filtrate was concentrated. The residue was recrystallized from EtOAc and hexane, the solid was collected by filtration and washed with hexane. The product was obtained (828 mg, 51%) as a solid: 1H NMR (400 MHz, DMSO-d6) δ ppm: 11.43 (1H, s), 8.31 (1H, d, J=5.05 Hz), 7.72 (1H, s), 7.66 (1H, d, J=2.27 Hz), 7.11 (1H, t, J=5.31 Hz), 7.06 (1H, dd, J=8.59, 2.78 Hz), 6.87 (1H, d, J=8.59 Hz), 4.99 (2H, s), 3.89 (3H, s); LC/MS (M+H)+: 378. HPLC ret. time (Condition E): 1.45 min.

Workup

  1. custompressurized to 140 psi in a steel bomb reactor
  2. stirringstirred overnight
  3. customreaction
  4. filtrationThe reaction was filtered through Celite
  5. washwashed with THF and DCM
  6. concentrationthe filtrate was concentrated
  7. customThe residue was recrystallized from EtOAc and hexane
  8. filtrationthe solid was collected by filtration
  9. washwashed with hexane
  10. customThe product was obtained (828 mg, 51%) as a solid
  11. custom1.45 min.

Sources & evidence

ORD record
ord-109eae02bf8348a99ea209ed067e15b1
Source dataset
uspto-grants-2012_04
Patent number
US08148400B2

Reaction notes

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