Pyridine → US10023592, Example 367

HRID 575801Notes

Reaction equation

HRID 575801 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([O:19][C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][C:21]=2[F:27])=[C:6]([C:8]2[N:13]3[CH:14]=[N:15][CH:16]=[C:12]3[C:11](=[O:17])[N:10]([CH3:18])[CH:9]=2)[CH:7]=1.N1C=CC=CC=1.[CH3:34][S:35](Cl)(=[O:37])=[O:36]>C1COCC1>[F:27][C:21]1[CH:22]=[C:23]([F:26])[CH:24]=[CH:25][C:20]=1[O:19][C:5]1[CH:4]=[CH:3][C:2]([NH:1][S:35]([CH3:34])(=[O:37])=[O:36])=[CH:7][C:6]=1[C:8]1[N:13]2[CH:14]=[N:15][CH:16]=[C:12]2[C:11](=[O:17])[N:10]([CH3:18])[CH:9]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 31297Methanesulfonyl chlorideHCID 1180221575-[5-Amino-2-(2,4-difluorophenoxyl)phenyl]-7-methylimidazo[1,5-a]pyrazin-8-one

Product 1

HCID 118021905US10023592, Example 367Yield 44.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of the title compound from Example 129, Step 2 (140 mg, 0.38 mmol) in THF (20 ml) was added pyridine (152 mg, 1.90 mmol). Then methanesulfonyl chloride (48 mg, 0.46 mmol) was added to the solution at 0° C. The solution was allowed to warm up to room temperature and heated to reflux for overnight. The reaction mixture was concentrated under reduced pressure to yield the crude product that was purified by prep-HPLC to give the title compound (75.26 mg, 44%) as a yellow solid. 1H NMR (CDCl3, 400 MHz) δ 8.60 (s, 1H), 8.15 (s, 1H), 7.50 (d, J=2.8 Hz, 1H), 7.30 (dd, J=8.8, 2.4 Hz, 1H), 7.18 (td, J=8.8, 5.3 Hz, 1H), 7.00-6.88 (m, 2H), 6.83 (s, 1H), 6.78 (d, J=8.8 Hz, 1), 3.60 (s, 3H), 3.03 (s, 3H). LCMS: 447.0 (M+1)+.

Workup

  1. temperatureheated
  2. temperatureto reflux for overnight
  3. concentrationThe reaction mixture was concentrated under reduced pressure
  4. customto yield the crude product that
  5. customwas purified by prep-HPLC

Sources & evidence

ORD record
ord-1d766e25f8be41fb9108f4548c765dcf
Source dataset
uspto-grants-2015_05
Patent number
US09034900B2

Reaction notes

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