Ammonium Chloride → 2-methyl-6-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)-4-(pyrazolo[1,5-a]pyridin-3-ylmethylamino)pyridazin-3(2H)-one

HRID 530810Notes

Reaction equation

HRID 530810 reaction equation
Br[CH2:2][C:3]1[CH:4]=[N:5][N:6]2[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=12.[NH2:12][C:13]1[C:14](=[O:33])[N:15]([CH3:32])[N:16]=[C:17]([O:19][CH2:20][C@H:21]2[CH2:23][C@@H:22]2[C:24]2[CH:29]=[CH:28][C:27](OC)=[CH:26][N:25]=2)[CH:18]=1.[NH4+].[Cl-].[CH3:36]O.O>C(Cl)Cl.C(#N)C.O>[CH3:32][N:15]1[C:14](=[O:33])[C:13]([NH:12][CH2:2][C:3]2[CH:4]=[N:5][N:6]3[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=23)=[CH:18][C:17]([O:19][CH2:20][C@H:21]2[CH2:23][C@@H:22]2[C:24]2[CH:29]=[CH:28][C:27]([CH3:36])=[CH:26][N:25]=2)=[N:16]1

Participants

8

Reactant 4

HCID 25517Ammonium ChlorideHCID 22242641Methanol--water (1/1)HCID 768522023-(Bromomethyl)pyrazolo[1,5-a]pyridineHCID 904544004-amino-6-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyridazin-3(2H)-one

Product 1

HCID 862705852-methyl-6-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)-4-(pyrazolo[1,5-a]pyridin-3-ylmethylamino)pyridazin-3(2H)-one

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

To the solution of 3-(bromomethyl)pyrazolo[1,5-a]pyridine (3) (4 mL, 0.27 mmol, 0.0675 mmol/ml) in DCM (4 mL) was added TEA (33 mg, 0.33 mmol) and 4-amino-6-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyridazin-3(2H)-one (50 mg, 0.165 mmol) at room temperature and stirred for 1 h, then 10 mL sat. NH4Cl was added, extracted with EtOAc (3×10 mL). The combined organic phase were dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by reverse phase chromatography (X bridge Prep C18OBD, 40-60% acetonitrile in water with 10 mmol NH4HCO3 modifier) to afford the compound as an oil. 1H NMR (400 MHz, MeOD) δ 8.47 (d, 1H), 8.03 (d, 1H), 7.96 (s, 1H), 7.67 (d, 1H), 7.26-7.11 (m, 3H), 6.87-6.84 (m, 1H), 5.85 (s, 1H), 4.50 (s, 2H), 4.17-4.13 (m, 1H), 4.02-3.97 (m, 1H), 3.82 (s, 3H), 3.59 (s, 3H), 2.06-2.02 (m, 1H), 1.75-1.71 (m, 1H), 1.17-1.13 (m, 1H) 1.02-0.99 (m, 1H); LRMS m/z (M+H) 433.1 found, 433.15 required.

Workup

  1. extractionextracted with EtOAc (3×10 mL)
  2. dry with materialThe combined organic phase were dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-26055b1b4b5b40e8bc16e45722ed801c
Source dataset
uspto-grants-2016_05
Patent number
US09353104B2

Reaction notes

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