6-fluoropyridine-2-carboxamide → 6-{[4-(6,6-Dimethyl-4-oxo-4,5,6,7-tetrahydro[1,3]thiazolo[5,4-c]pyridin-2-yl)-3,4-dihydro-2h-1,4-benzoxazin-6-yl]oxy}pyridine-2-carboxamide

HRID 885987Notes

Reaction equation

HRID 885987 reaction equation
[CH3:1][C:2]1([CH3:23])[NH:7][C:6](=[O:8])[C:5]2[S:9][C:10]([N:12]3[C:17]4[CH:18]=[C:19]([OH:22])[CH:20]=[CH:21][C:16]=4[O:15][CH2:14][CH2:13]3)=[N:11][C:4]=2[CH2:3]1.F[C:25]1[CH:30]=[CH:29][CH:28]=[C:27]([C:31]([NH2:33])=[O:32])[N:26]=1.CC(C)([O-])C.[Na+]>C1COCC1>[CH3:1][C:2]1([CH3:23])[NH:7][C:6](=[O:8])[C:5]2[S:9][C:10]([N:12]3[C:17]4[CH:18]=[C:19]([O:22][C:25]5[N:26]=[C:27]([C:31]([NH2:33])=[O:32])[CH:28]=[CH:29][CH:30]=5)[CH:20]=[CH:21][C:16]=4[O:15][CH2:14][CH2:13]3)=[N:11][C:4]=2[CH2:3]1

Participants

5

Reactant 3

HCID 27693956-fluoropyridine-2-carboxamideHCID 23676156Sodium t-butoxideHCID 671855836,6-Dimethyl-2-(6-hydroxy-2,3-dihydrobenzo[1,4]oxazin-4-yl)-6,7-dihydro-[1,3]thiazolo[5,4-c]pyridin-4(5h)-one

Product 1

HCID 685993246-{[4-(6,6-Dimethyl-4-oxo-4,5,6,7-tetrahydro[1,3]thiazolo[5,4-c]pyridin-2-yl)-3,4-dihydro-2h-1,4-benzoxazin-6-yl]oxy}pyridine-2-carboxamideYield 12%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
145 °C

Procedure

To a solution of Example 57 (75 mg, 0.227 mmol) in THF (4 mL) was added 2-fluoro-6-pyridinecarboxamide (64 mg, 0.453 mmol) and sodium tert-butoxide (87 mg, 0.906 mmol). The reaction was heated to 145° C. under microwave irradiation for 50 minutes then cooled to r.t. The mixture was partitioned between DCM (50 mL) and water (50 mL); the organic phase was washed with brine (50 mL), dried (MgSO4), and concentrated in vacuo. The residue was purified by preparative HPLC (Method 6) to give the title compound (12 mg, 12%) as a white solid. δH (CDCl3) 8.02 (1H, d, J 2.6 Hz), 7.91 (1H, dd, J 7.2 and 0.9 Hz), 7.85 (1H, t, J 7.9 Hz), 7.08 (1H, dd, J 7.9 and 0.9 Hz), 6.98 (1H, d, J 8.9 Hz), 6.85 (1H, dd, J 8.9 and 2.6 Hz), 4.27-4.43 (2H, m), 4.05-4.17 (2H, m), 2.83 (2H, s), 1.37 (6H, s). LCMS (ES+) 452.0 (M+H)+, RT 2.85 minutes (Method 1).

Workup

  1. temperaturethen cooled to r.t
  2. customThe mixture was partitioned between DCM (50 mL) and water (50 mL)
  3. washthe organic phase was washed with brine (50 mL)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by preparative HPLC (Method 6)

Sources & evidence

ORD record
ord-f85adebf94414c5b91507717e391bacd
Source dataset
uspto-grants-2012_08
Patent number
US08242116B2

Reaction notes

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