Pyrrolidine → 2-[4-(2-hydroxyethyl)piperazin-1-yl]-N-[2,4-bis(pyrrolidin-1-yl)-6-methylpyridin-3-yl]acetamide

HRID 348569Notes

Reaction equation

HRID 348569 reaction equation
[OH:1][CH2:2][CH2:3][N:4]1[CH2:9][CH2:8][N:7]([CH2:10][C:11]([NH:13][C:14]2[C:15](Br)=[N:16][C:17]([CH3:21])=[CH:18][C:19]=2Br)=[O:12])[CH2:6][CH2:5]1.[NH:23]1[CH2:27][CH2:26][CH2:25][CH2:24]1>>[OH:1][CH2:2][CH2:3][N:4]1[CH2:9][CH2:8][N:7]([CH2:10][C:11]([NH:13][C:14]2[C:15]([N:23]3[CH2:27][CH2:26][CH2:25][CH2:24]3)=[N:16][C:17]([CH3:21])=[CH:18][C:19]=2[N:23]2[CH2:27][CH2:26][CH2:25][CH2:24]2)=[O:12])[CH2:6][CH2:5]1

Participants

3

Reactant 2

HCID 31268PyrrolidineHCID 116406602-[4-(2-Hydroxyethyl)piperazin-1-yl]-N-[2,4-dibromo-6-methyl-3-pyridyl]acetamide

Product 1

HCID 210873432-[4-(2-hydroxyethyl)piperazin-1-yl]-N-[2,4-bis(pyrrolidin-1-yl)-6-methylpyridin-3-yl]acetamide

Procedure

2-[4-(2-Hydroxyethyl)piperazin-1-yl]-N-[2,4-dibromo-6-methyl-3-pyridyl]acetamide (1.00 g, 2.29 mmol) was dissolved in pyrrolidine (10 mL), and the solution was subjected to reflux for 4 days. The reaction mixture was concentrated under reduced pressure, and the residue was subjected to separation through silica gel column chromatography (developer: hexane:acetone=2:1), to thereby yield a crude product of 2-[4-(2-hydroxyethyl)piperazin-1-yl]-N-[2,4-bis(pyrrolidin-1-yl)-6-methyl-3-pyridyl]acetamide (1.22 g) as a brown foamed substance. The crude product was dissolved in pyridine (20 mL), and acetic anhydride (10 mL) was added thereto under cooling with ice, followed by stirring for 14 hours at room temperature. The reaction mixture was concentrated under reduced pressure. Toluene (70 mL) was added to the residue and then evaporated three times, followed by purification through silica gel column chromatography (developer: chloroform:methanol=20:1→chloroform:ammonia-saturated methanol=50:1→chloroform:ammonia-saturated methanol=20:1), to thereby yield a brown oil (1.05 g). The oil was dissolved in ammonia-saturated methanol (30 mL), and the solution was stirred for 14 hours at room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was purified through silica gel column chromatography (developer: chloroform:ammonia-saturated methanol=100:1→chloroform:ammonia-saturated methanol=20:1), to thereby yield 2-[4-(2-hydroxyethyl)piperazin-1-yl]-N-[2,4-bis(pyrrolidin-1-yl)-6-methyl-3-pyridyl]acetamide (911 mg, yield 95%) as a pale brown foamed susbtance.

Workup

  1. temperatureto reflux for 4 days
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. customthe residue was subjected to separation through silica gel column chromatography (developer: hexane:acetone=2:1)

Sources & evidence

ORD record
ord-0701459fcfa747909cab5635eb5aafc5
Source dataset
uspto-grants-2007_02
Patent number
US07176306B2

Reaction notes

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