Sulfuric acid magnesium salt (1:1) → 1-(7-Aza-bicyclo[2.2.1]hept-7-yl)-2-(2-(3,5-dimethylphenyl)-3-{2-[(5-pyridin-3-yl-thiophen-2-ylmethyl)amino]ethyl}-1H-indol-5-yl)-2-methylpropan-1-one

HRID 1421532Notes

Reaction equation

HRID 1421532 reaction equation
[NH2:1][CH2:2][CH2:3][C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([C:13]([CH3:24])([CH3:23])[C:14]([N:16]3[CH:20]4[CH2:21][CH2:22][CH:17]3[CH2:18][CH2:19]4)=[O:15])[CH:11]=2)[NH:6][C:5]=1[C:25]1[CH:30]=[C:29]([CH3:31])[CH:28]=[C:27]([CH3:32])[CH:26]=1.S([O-])([O-])(=O)=O.[Mg+2].[N:39]1[CH:44]=[CH:43][CH:42]=[C:41]([C:45]2[S:49][C:48]([CH:50]=O)=[CH:47][CH:46]=2)[CH:40]=1.C([BH3-])#N.[Na+]>C(Cl)(Cl)Cl.CO.C(O)(=O)C>[CH:17]12[N:16]([C:14](=[O:15])[C:13]([C:10]3[CH:11]=[C:12]4[C:7](=[CH:8][CH:9]=3)[NH:6][C:5]([C:25]3[CH:30]=[C:29]([CH3:31])[CH:28]=[C:27]([CH3:32])[CH:26]=3)=[C:4]4[CH2:3][CH2:2][NH:1][CH2:50][C:48]3[S:49][C:45]([C:41]4[CH:40]=[N:39][CH:44]=[CH:43][CH:42]=4)=[CH:46][CH:47]=3)([CH3:24])[CH3:23])[CH:20]([CH2:19][CH2:18]1)[CH2:21][CH2:22]2

Participants

8

Reactant 4

HCID 24083Sulfuric acid magnesium salt (1:1)HCID 5003444Sodium cyanoborohydrideHCID 108994275-(Pyridin-3-yl)thiophene-2-carbaldehydeHCID 117617912-[3-(2-Aminoethyl)-2-(3,5-dimethylphenyl)-1H-indol-5-yl]-1-(7-azabicyclo[2.2.1]hept-7-yl)-2-methyl-propan-1-one

Product 1

HCID 99386751-(7-Aza-bicyclo[2.2.1]hept-7-yl)-2-(2-(3,5-dimethylphenyl)-3-{2-[(5-pyridin-3-yl-thiophen-2-ylmethyl)amino]ethyl}-1H-indol-5-yl)-2-methylpropan-1-one

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 887MethanolSolventHCID 6212ChloroformSolvent

Procedure

To a solution of 2-[3-(2-aminoethyl)-2-(3,5-dimethylphenyl)-1H-indol-5-yl]-1-(7-azabicyclo [2.2.1]hept-7-yl)-2-methyl-propan-1-one (15 mg in a mixture of 1.0 mL dry chloroform and 0.10 mL methanol) at 0° C. was added 25 mg magnesium sulfate followed by 5-pyridin-3-yl-thiophene-2-carbaldehyde (9.3 mg) and the mixture stirred at low temperature. After 40 minutes, 0.070 mL of acetic acid were added followed by a solution of sodium cyanoborohydride (4.4 mg in 0.10 mL methanol) and the mixture allowed to warm to room temperature. After 20 hours, the reaction was quenched by the addition of saturated aqueous sodium bicarbonate, extracted with methylene chloride and the combined organics washed sequentially with water and brine. Purification of the concentrate by preparative tlc on silica gel (ethyl acetate) followed by preparative reverse phase HPLC (water:acetonitrile, 60:40) gave the title compound (3.2 mg). MASS: 602 (M+H)

Workup

  1. waitAfter 20 hours
  2. customthe reaction was quenched by the addition of saturated aqueous sodium bicarbonate
  3. extractionextracted with methylene chloride
  4. washthe combined organics washed sequentially with water and brine
  5. customPurification of the
  6. concentrationconcentrate by preparative tlc on silica gel (ethyl acetate)

Sources & evidence

ORD record
ord-9272fd7253ab4c61bc53ac43f755d12a
Source dataset
uspto-grants-2000_06
Patent number
US06077858

Reaction notes

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