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Sodium hydride → HCID 67981025, compound

HRID 1520063
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Reaction equation

HRID 1520063 reaction equation
[H-].[Na+].[F:3][C:4]1[CH:5]=[C:6]([C:11]2[CH:12]=[CH:13][C:14](=[O:17])[NH:15][N:16]=2)[CH:7]=[C:8]([F:10])[CH:9]=1.Br[CH2:19][C:20]1[CH:21]=[C:22]2[C:26](=[CH:27][CH:28]=1)[N:25](C(OC(C)(C)C)=O)[N:24]=[C:23]2[C:36]1[N:37]=[N:38][N:39]([C:41]2[CH:46]=[CH:45][C:44]([C:47]([O:49]C)=[O:48])=[CH:43][CH:42]=2)[CH:40]=1.C([O-])(O)=O.[Na+]>CN(C=O)C.[OH-].[Na+].CS(C)=O>[F:3][C:4]1[CH:5]=[C:6]([C:11]2[CH:12]=[CH:13][C:14](=[O:17])[N:15]([CH2:19][C:20]3[CH:21]=[C:22]4[C:26](=[CH:27][CH:28]=3)[NH:25][N:24]=[C:23]4[C:36]3[N:37]=[N:38][N:39]([C:41]4[CH:46]=[CH:45][C:44]([C:47]([OH:49])=[O:48])=[CH:43][CH:42]=4)[CH:40]=3)[N:16]=2)[CH:7]=[C:8]([F:10])[CH:9]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 4

HCID 24758Sodium hydrideHCID 516892Sodium Bicarbonate2×HCID 252417496-(3,5-difluorophenyl)-2H-pyridazin-3-oneHCID 67981095tert-butyl 5-(bromomethyl)-3-{1-[4-(methoxycarbonyl)phenyl]-1H-1,2,3-triazol-4-yl}-1H-indazole-1-carboxylate

Product 1

HCID 67981025HCID 67981025, compoundYield 109.2%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 6228DimethylformamideSolvent2×HCID 14798Sodium HydroxideSolvent

Procedure

Sodium hydride (34. mg; 0.78 mmol; 2.0 eq.) was added in one portion to a solution of 6-(3,5-Difluoro-phenyl)-2H-pyridazin-3-one (106 mg; 0.51 mmol; 1.3 eq.) in DMF (3 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 (392 mg; 0.38 mmol; 1.0 eq.) in DMF (3 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 to give a yellow solid. This solid was redissolved in NaOH (5N, 0.5 mL) and DMSO (2 mL) and heated in MW for 10 min at 80° C. Reaction mixture was poured in a saturated solution of NaHCO3 and washed with EtOAc. The basic aqueous phase was acidified to pH 1 with 1N HCl and extracted with EtOAc. Combined organic phases were washed with brine, dried over magnesium sulfate, filtered and concentrated to give the title compound as a yellow solid (218 mg, 100%). 1H NMR (300 MHz, DMSO-d6) δ 13.43 (s, 1H), 9.44 (s, 1H), 8.47 (s, 1H), 8.29-8.09 (m, 6H), 7.68 (d, J=7.2 Hz, 2H), 7.63-7.47 (m, 2H), 7.40-7.30 (m, 1H), 7.14 (d, J=9.8 Hz, 1H), 5.52 (s, 2H). HPLC (Condition A): Rt 3.87 min (purity 52.8%). MS (ESI+): 526.2, MS (ESI−): 524.2.

Workup

  1. extractionextracted with EtOAc
  2. dry with materialCombined organic phases were dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto give a yellow solid
  6. customReaction mixture
  7. washwashed with EtOAc
  8. extractionextracted with EtOAc
  9. washCombined organic phases were washed with brine
  10. dry with materialdried over magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-eba8eab6e62647f497ccc43a361d784a
Source dataset
uspto-grants-2015_07
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09073892B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes