Potassium Hydroxide → HCID 10990898, compound

HRID 1004625Notes

Reaction equation

HRID 1004625 reaction equation
COC([N:5]1[CH2:12][C@@H:11]2[C@@H:7]([N:8]([CH2:13][CH2:14][C:15]3[C:23]4[C:18](=[CH:19][CH:20]=[C:21]([N:24]5[CH:28]=[N:27][N:26]=[CH:25]5)[CH:22]=4)[NH:17][CH:16]=3)[CH2:9][CH2:10]2)[CH2:6]1)=O.O.NN.[OH-].[K+]>C(O)CO>[N:26]1[N:27]=[CH:28][N:24]([C:21]2[CH:22]=[C:23]3[C:18](=[CH:19][CH:20]=2)[NH:17][CH:16]=[C:15]3[CH2:14][CH2:13][N:8]2[CH2:9][CH2:10][C@@H:11]3[CH2:12][NH:5][CH2:6][C@H:7]23)[CH:25]=1

Participants

5

Reactant 3

HCID 14797Potassium HydroxideHCID 24654Hydrazine hydrate (1:1)HCID 131721764HCID 131721764, compound

Product 1

HCID 10990898HCID 10990898, compoundYield 62%

Reagents, catalysts & solvents 1

HCID 174Ethylene GlycolSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of cis-1-[2-(5-[1,2,4]triazol-4-yl-1H-indol-3-yl)-ethyl)-hexahydro-pyrrolo[3,4-b]pyrrole-5-carboxylic acid methyl ester (enantiomer B) (1.9 g, 5.0 mmol), hydrazine hydrate (1.2 ml, 25 mmol) and powdered potassium hydroxide (3.4 g, 61 mmol) in dry ethylene glycol (25 ml) was stirred and heated at 100° C. under nitrogen for 16 hours. Upon cooling the mixture was partitioned between dichloromethane and water. The aqueous was further extracted with dichloromethane ) and n-butanol (×2). The combined extracts were evaporated and the residue was purified by chromatography on neutral alumina (grade III) (dry loaded), eluting with CH2Cl2 /MeOH/NH3 (95:5:0.5) to give the title amine (1.0 g, 62%) as a pale yellow foam; δ (250 MHz, d6 -DMSO) 1.33-1.48 (1H, m), 1.90-2.04 (1H, m), 2.14-2.26 (1H, m), 2.40 (1H, dd, J=11.8, 4.9 Hz), 2.56-2.96 (11H, m), 3.07 (1H, t, J=7.4 Hz), 7.30 (1H, dd, J=8.6, 2.1 Hz, Ar--H), 7.34 (1H, d, J=2.2 Hz, Ar--H), 7.48 (1H, d, J=8.6 Hz, Ar--H), 7.79 (1H, d, J=2.0 Hz, Ar--H), 9.03 (2H, s, Triazole-H), 11.11 (1H, br s, NH).

Workup

  1. temperatureUpon cooling the mixture
  2. customwas partitioned between dichloromethane and water
  3. extractionThe aqueous was further extracted with dichloromethane ) and n-butanol (×2)
  4. customThe combined extracts were evaporated
  5. customthe residue was purified by chromatography on neutral alumina (grade III) (dry loaded)
  6. washeluting with CH2Cl2 /MeOH/NH3 (95:5:0.5)

Sources & evidence

ORD record
ord-00798b5174724f218e8c25a9fca9ba1e
Source dataset
uspto-grants-2000_04
Patent number
US06051591

Reaction notes

Loading…