Isoamylamine → HCID 178424944, compound

HRID 2174006Notes

Reaction equation

HRID 2174006 reaction equation
[OH:1][C:2]([C:27]1[NH:31][C:30]2[CH:32]=[CH:33][C:34]([C:36]#[N:37])=[CH:35][C:29]=2[N:28]=1)([C:4]1[C:12]([CH:13]([CH3:15])[CH3:14])=[CH:11][C:10]([CH3:16])=[C:9]2[C:5]=1[CH:6]=[CH:7][N:8]2S(C1C=CC(C)=CC=1)(=O)=O)[CH3:3].OC(C1NC2C=CC(C#N)=CC=2N=1)(C1C(CCC)=CC(C)=C2C=1C=CN2S(C1C=CC(C)=CC=1)(=O)=O)C.C(N)CC(C)C.[OH-].[K+]>C(Cl)Cl>[OH:1][C:2]([C:27]1[NH:31][C:30]2[CH:32]=[CH:33][C:34]([C:36]#[N:37])=[CH:35][C:29]=2[N:28]=1)([C:4]1[C:12]([CH:13]([CH3:15])[CH3:14])=[CH:11][C:10]([CH3:16])=[C:9]2[C:5]=1[CH:6]=[CH:7][NH:8]2)[CH3:3]

Participants

6

Reactant 4

HCID 7894IsoamylamineHCID 14797Potassium HydroxideHCID 178427337HCID 178427337, compoundHCID 178438887HCID 178438887, compound

Product 1

HCID 178424944HCID 178424944, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of (±)-2-(1-hydroxy-1-(5-isopropyl-7-methyl-1-tosyl-1H-indol-4-yl)ethyl)-1H-benzo[d]imidazole-5-carbonitrile and (±)-2-(1-hydroxy-1-(7-methyl-5-propyl-1-tosyl-1H-indol-4-yl)ethyl)-1H-benzo[d]imidazole-5-carbonitrile (110 mg, 0.215 mmol), isoamylamine (94 mg, 1.073 mmol), and KOH (60.2 mg, 1.073 mmol) was stirred at 100° C. for 0.75 h under the microwave irradiation. The reaction mixture was diluted with CH2Cl2. The mixture was filtered through SiO2. The SiO2 cake was washed with a mixture of CH2Cl2/MeOH (c.a. 6/1). Combined organic solution was concentrated and purified by silica gel flash column chromatography (CH2Cl2/EtOAc=82/18, isocratic) to give (±)-2-(1-hydroxy-1-(5-isopropyl-7-methyl-1H-indol-4-yl)ethyl)-1H-benzo[d]imidazole-5-carbonitrile as a pure isomeric form. 1H NMR (400 MHz, ACETONITRILE-d3 with about 5 μL TFA) δ ppm 9.28 (br. s., 1H), 8.05 (s, 1H), 7.73 (d, J=8.60 Hz, 1H), 7.69 (dd, J=1.30, 8.60 Hz, 1H), 7.19 (dd, J=2.80, 2.90 Hz, 1H), 7.00 (s, 1H), 6.66 (dd, J=2.30, 3.00 Hz, 1H), 2.90-3.06 (m, 1H), 2.47 (s, 3H), 2.28 (s, 3H), 0.95 (d, J=6.82 Hz, 3H), 0.92 (d, J=6.57 Hz, 3H). HRMS calcd. for C22H22N4O (M+H)+ 359.1867. found 359.1865.

Workup

  1. filtrationThe mixture was filtered through SiO2
  2. washThe SiO2 cake was washed with a mixture of CH2Cl2/MeOH (c.a. 6/1)
  3. concentrationCombined organic solution was concentrated
  4. custompurified by silica gel flash column chromatography (CH2Cl2/EtOAc=82/18, isocratic)

Sources & evidence

ORD record
ord-3e0b8444048b4ff2b14e7c06d153d81d
Source dataset
uspto-grants-2015_06
Patent number
US09056874B2

Reaction notes

Loading…