Sodium hydride → tert-butyl 3-{1-[4-(methoxycarbonyl)phenyl]-1H-1,2,3-triazol-4-yl}-5-[(6-oxo-3-pyridin-4-ylpyridazin-1(6H)-yl)methyl]-1H-indazole-1-carboxylate

HRID 1520067Notes

Reaction equation

HRID 1520067 reaction equation
[H-].[Na+].[N:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:10]=[CH:11][C:12](=[O:15])[NH:13][N:14]=2)=[CH:5][CH:4]=1.Br[CH2:17][C:18]1[CH:19]=[C:20]2[C:24](=[CH:25][CH:26]=1)[N:23]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[N:22]=[C:21]2[C:34]1[N:35]=[N:36][N:37]([C:39]2[CH:44]=[CH:43][C:42]([C:45]([O:47][CH3:48])=[O:46])=[CH:41][CH:40]=2)[CH:38]=1.C([O-])(O)=O.[Na+]>CN(C=O)C>[CH3:48][O:47][C:45]([C:42]1[CH:43]=[CH:44][C:39]([N:37]2[CH:38]=[C:34]([C:21]3[C:20]4[C:24](=[CH:25][CH:26]=[C:18]([CH2:17][N:13]5[C:12](=[O:15])[CH:11]=[CH:10][C:9]([C:6]6[CH:7]=[CH:8][N:3]=[CH:4][CH:5]=6)=[N:14]5)[CH:19]=4)[N:23]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[N:22]=3)[N:35]=[N:36]2)=[CH:40][CH:41]=1)=[O:46]

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 27276126-(Pyridin-4-yl)pyridazin-3(2H)-oneHCID 67981095tert-butyl 5-(bromomethyl)-3-{1-[4-(methoxycarbonyl)phenyl]-1H-1,2,3-triazol-4-yl}-1H-indazole-1-carboxylate

Product 1

HCID 68061164tert-butyl 3-{1-[4-(methoxycarbonyl)phenyl]-1H-1,2,3-triazol-4-yl}-5-[(6-oxo-3-pyridin-4-ylpyridazin-1(6H)-yl)methyl]-1H-indazole-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Sodium hydride (106 mg; 2.43 mmol; 7.4 eq.) was added in one portion to a solution of 6-pyridin-4-ylpyridazin-3(2H)-one (176 mg; 1.02 mmol; 3.1 eq.) in DMF (6 mL). After 10 min a solution of tert-butyl 5-(bromomethyl)-3-{1-[4-(methoxycarbonyl)phenyl]-1H-1,2,3-triazol-4-yl}-1H-indazole-1-carboxylate (565 mg; 0.33 mmol; 1.0 eq.) in DMF (6 mL) was added dropwise over 2 min and the reaction solution stirred for 4 h at RT. The reaction mixture was then poured into saturated solution of NaHCO3 and extracted with EtOAc. Combined organic phases were dried over magnesium sulfate, filtered and concentrated. The crude was purified by preparative HPLC to give the title compound as a yellow solid. 1H NMR (300 MHz, DMSO-d6) δ 9.69 (s, 1H), 8.75-8.62 (m, 3H), 8.30 (d, J=8.8 Hz, 2H), 8.24-8.18 (m, 3H), 8.15 (d, J=9.2 Hz, 1H), 7.93 (dd, J=1.6, 4.6 Hz, 2H), 7.78-7.72 (m, 1H), 7.19 (d, J=9.8 Hz, 1H), 5.59 (s, 2H), 3.92 (s, 3H), 1.68 (s, 9H). MS (ESI+): 605.3.

Workup

  1. extractionextracted with EtOAc
  2. dry with materialCombined organic phases were dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude was purified by preparative HPLC

Sources & evidence

ORD record
ord-e355d4ed29d940f0b124e582108779d7
Source dataset
uspto-grants-2015_07
Patent number
US09073892B2

Reaction notes

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