Potassium Sodium Tartrate → (2-(1-(2,2-dimethoxyethyl)-1H-indazol-5-yloxy)-5-fluorophenyl)methanamine

HRID 1666756Notes

Reaction equation

HRID 1666756 reaction equation
[CH3:1][O:2][CH:3]([O:24][CH3:25])[CH2:4][N:5]1[C:13]2[C:8](=[CH:9][C:10]([O:14][C:15]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:16]=3[C:17]#[N:18])=[CH:11][CH:12]=2)[CH:7]=[N:6]1.[H-].[Al+3].[Li+].[H-].[H-].[H-].[C@H](O)(C([O-])=O)[C@@H](O)C([O-])=O.[Na+].[K+].[Al]>C1COCC1>[CH3:25][O:24][CH:3]([O:2][CH3:1])[CH2:4][N:5]1[C:13]2[C:8](=[CH:9][C:10]([O:14][C:15]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:16]=3[CH2:17][NH2:18])=[CH:11][CH:12]=2)[CH:7]=[N:6]1

Participants

6

Reactant 4

HCID 9357Potassium Sodium TartrateHCID 5359268AluminumHCID 21226445Aluminium lithium hydrideHCID 666711532-(1-(2,2-dimethoxyethyl)-1H-indazol-5-yloxy)-5-fluorobenzonitrile

Product 1

HCID 57552285(2-(1-(2,2-dimethoxyethyl)-1H-indazol-5-yloxy)-5-fluorophenyl)methanamineYield 97%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

2-(1-(2,2-Dimethoxyethyl)-1H-indazol-5-yloxy)-5-fluorobenzonitrile (3.80 g, 11.13 mmol) in THF (100 mL) was added dropwise to a stirred 0° C. suspension of lithium aluminum hydride (0.6338 g, 16.70 mmol) in THF (100 mL). The reaction mixture was maintained at 0° C. until complete addition of the starting material was achieved. The reaction mixture was warmed to room temperature and stirred until complete consumption of starting material was seen by HPLC analysis. The reaction mixture was added dropwise to a stirred room temperature solution of saturated aqueous Rochelle's salt. The two phase mixture was rapidly stirred for 30 minutes until the aluminum salts were in solution. The layers were separated and the aqueous layer extracted with more EtOAc. The combined organics were dried (MgSO4) and concentrated under reduced pressure to afford 3.73 g (97%) of the crude product, which was used without further purification. MS (APCI+) m/z 346 (M+1) was detected. 1H NMR (400 MHz, CDCl3) δ 7.90 (s, 1H), 7.48 (d, 1H, J=9 Hz), 6.9-7.15 (m, 5H), 4.76 (t, 1H, J=5.3 Hz), 4.49 (d, 2H, J=5.3 Hz), 3.88 (s, 2H), 3.36 (s, 6H).

Workup

  1. temperatureThe reaction mixture was warmed to room temperature
  2. customThe layers were separated
  3. extractionthe aqueous layer extracted with more EtOAc
  4. dry with materialThe combined organics were dried (MgSO4)
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-efca0902ae7546d7b858979a6cc03706
Source dataset
uspto-grants-2011_10
Patent number
US08044083B2

Reaction notes

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