Aluminium lithium hydride → N-[2-({2-Amino-1-[1-(4-fluorophenyl)cyclobutyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}oxy)ethyl]propane-1-sulfonamide

HRID 1850856Notes

Reaction equation

HRID 1850856 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].[F:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2([CH:18]3[C:27]4[C:22](=[CH:23][CH:24]=[C:25]([O:28][CH2:29][CH2:30][NH:31][S:32]([CH2:35][CH2:36][CH3:37])(=[O:34])=[O:33])[CH:26]=4)[CH2:21][CH2:20][N:19]3[N:38]=O)[CH2:17][CH2:16][CH2:15]2)=[CH:10][CH:9]=1>O1CCCC1>[NH2:38][N:19]1[CH2:20][CH2:21][C:22]2[C:27](=[CH:26][C:25]([O:28][CH2:29][CH2:30][NH:31][S:32]([CH2:35][CH2:36][CH3:37])(=[O:34])=[O:33])=[CH:24][CH:23]=2)[CH:18]1[C:14]1([C:11]2[CH:10]=[CH:9][C:8]([F:7])=[CH:13][CH:12]=2)[CH2:15][CH2:16][CH2:17]1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 44465811N-[2-({1-[1-(4-Fluorophenyl)cyclobutyl]-2-nitroso-1,2,3,4-tetrahydroisoquinolin-7-yl}oxy)ethyl]propane-1-sulfonamide

Product 1

HCID 66868979N-[2-({2-Amino-1-[1-(4-fluorophenyl)cyclobutyl]-1,2,3,4-tetrahydroisoquinolin-7-yl}oxy)ethyl]propane-1-sulfonamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A reaction vessel was charged with lithiumaluminium hydride (23.5 mg, 0.618 mmol) and dry tetrahydrofuran (1 mL). N-[2-({1-[1-(4-fluorophenyl)cyclobutyl]-2-nitroso-1,2,3,4-tetrahydroisoquinolin-7-yl}oxy)ethyl]propane-1-sulfonamide (49 mg, 0.103 mmol, cf. example 75) was added dropwise as a solution in dry tetrahydrofuran (1 mL) at 0° C. After the addition was completed the reaction mixture was stirred at room temperature for 1 h and then at 40-50° C. for 1 h. After cooling to room temperature the reaction mixture was poured on ice water (15 mL) and the aqueous phase was extracted with ethyl acetate (3×10 mL). The combined extracts were dried (MgSO4) and concentrated in vacuo. The crude product was purified by preparative HPLC (RP, acetonitrile, water). Yield: 1 mg (2.2 μmol, 2%)

Workup

  1. additionAfter the addition
  2. waitat 40-50° C. for 1 h
  3. temperatureAfter cooling to room temperature the reaction mixture
  4. additionwas poured on ice water (15 mL)
  5. extractionthe aqueous phase was extracted with ethyl acetate (3×10 mL)
  6. dry with materialThe combined extracts were dried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by preparative HPLC (RP, acetonitrile, water)

Sources & evidence

ORD record
ord-22214926f9c74979beb522b0118bfda3
Source dataset
uspto-grants-2015_02
Patent number
US08957089B2

Reaction notes

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