Water → (1R)-2-[(1,1-dimethyl-2-{7-[(1S)-1-methyl-2-morpholin-4-yl-2-oxoethoxy]-1H-indol-3-yl}ethyl)amino]-1-pyridin-3-ylethanol

HRID 1351986Notes

Reaction equation

HRID 1351986 reaction equation
[CH3:1][C:2]([NH2:25])([CH3:24])[CH2:3][C:4]1[C:12]2[C:7](=[C:8]([O:13][C@@H:14]([CH3:23])[C:15]([N:17]3[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)=[O:16])[CH:9]=[CH:10][CH:11]=2)[NH:6][CH:5]=1.O.[N:27]1[CH:32]=[CH:31][CH:30]=[C:29]([C@@H:33]2[CH2:35][O:34]2)[CH:28]=1>C(O)C>[CH3:1][C:2]([NH:25][CH2:35][C@@H:33]([C:29]1[CH:28]=[N:27][CH:32]=[CH:31][CH:30]=1)[OH:34])([CH3:24])[CH2:3][C:4]1[C:12]2[C:7](=[C:8]([O:13][C@@H:14]([CH3:23])[C:15]([N:17]3[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)=[O:16])[CH:9]=[CH:10][CH:11]=2)[NH:6][CH:5]=1

Participants

5

Reactant 3

HCID 962WaterHCID 13319559(S)-3-Oxiranyl-pyridine2×HCID 694581352-Methyl-1-{7-[(1S)-1-methyl-2-morpholin-4-yl-2-oxoethoxy]-1H-indol-3-yl}propan-2-amine

Product 1

HCID 69457281(1R)-2-[(1,1-dimethyl-2-{7-[(1S)-1-methyl-2-morpholin-4-yl-2-oxoethoxy]-1H-indol-3-yl}ethyl)amino]-1-pyridin-3-ylethanolYield 25%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
10 °C

Procedure

To a solution of 2-methyl-1-{7-[(1S)-1-methyl-2-morpholin-4-yl-2-oxoethoxy]-1H-indol-3-yl}propan-2-amine (68.4 mg, 0.198 mmol) in ethanol (4 mL)- water (0.4 mL) is added (R)-(pyridin-3-yl)oxirane (36.0 mg, 0.297 mmol), and the mixture is refluxed for 8 hours. To the reaction solution is added (R)-(pyridin-3-yl)oxirane (144.0 mg, 1.19 mmol) in 4 portions, and the mixture is heated with stirring at 100 to 1 10° C. in a sealed tube for 18 hours. After the reaction is completed, the solvent is evaporated under reduced pressure, and the obtained residue is purified by silica gel column chromatography (chloroform/methanol=20/1→10/1→chloroform/a saturated ammonia methanol=10/1) to give (1R)-2-[(1,1-dimethyl-2-{7-[(1S)-1-methyl-2-morpholin-4-yl-2-oxoethoxy]-1H-indol-3-yl}ethyl)amino]-1-pyridin-3-ylethanol (23.1 mg).

Workup

  1. temperaturethe mixture is refluxed for 8 hours
  2. temperaturethe mixture is heated
  3. customthe solvent is evaporated under reduced pressure
  4. customthe obtained residue is purified by silica gel column chromatography (chloroform/methanol=20/1→10/1→chloroform/a saturated ammonia methanol=10/1)

Sources & evidence

ORD record
ord-c612bab325474cfa8ede1a928a954bc9
Source dataset
uspto-grants-2007_05
Patent number
US07217724B2

Reaction notes

Loading…