Diethyl Ether → (2-(1-(4-fluorophenyl)-1H-indazol-5-yl)-2-phenylcyclopropyl)methanamine

HRID 218136Notes

Reaction equation

HRID 218136 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([C:17]4([C:22]5[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=5)[CH2:19][CH:18]4[C:20]#[N:21])=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:4][CH:3]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].C(OCC)C.C(O)(C(F)(F)F)=O>C1COCC1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([C:17]4([C:22]5[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=5)[CH2:19][CH:18]4[CH2:20][NH2:21])=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 6422Trifluoroacetic acidHCID 21226445Aluminium lithium hydrideHCID 592510952-(1-(4-fluorophenyl)-1H-indazol-5-yl)-2-phenylcyclopropanecarbonitrile

Product 1

HCID 68707146(2-(1-(4-fluorophenyl)-1H-indazol-5-yl)-2-phenylcyclopropyl)methanamineYield 50.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 2-(1-(4-fluorophenyl)-1H-indazol-5-yl)-2-phenylcyclopropanecarbonitrile (275 mg, 0.78 mmol) in anhydrous THF (10 mL) was added 1.0M lithium aluminum hydride in diethyl ether (2.0 mL, 2.0 mmol) portionwise at RT under nitrogen. After stirring at RT for 12 hr, the mixture was quenched with MeOH, poured into a 1N sodium brine, extracted with ethyl acetate (2×100 mL), dried (MgSO4), concentrated and purified by HPLC to give 142 mg (39% yield) of (2-(1-(4-fluorophenyl)-1H-indazol-5-yl)-2-phenylcyclopropyl)methanamine as the TFA salt. MS found: (M+H)+=358.

Workup

  1. customthe mixture was quenched with MeOH
  2. additionpoured into a 1N sodium brine
  3. extractionextracted with ethyl acetate (2×100 mL)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. custompurified by HPLC

Sources & evidence

ORD record
ord-1e7e6fd2147d4ae0944aaad295ed99fb
Source dataset
uspto-grants-2012_06
Patent number
US08198311B2

Reaction notes

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