Diisopropylethylamine → N-ethyl-4-(4-((6-oxo-5,6-dihydropyrido[2,3-e]pyrrolo[1,2-c]pyrimidin-3-yl)methyl)piperazin-1-yl)benzamide

HRID 44313

Reaction equation

HRID 44313 reaction equation
O[CH2:2][C:3]1[CH:16]=[N:15][C:6]2[C:7]3[N:8]([CH:12]=[CH:13][CH:14]=3)[C:9](=[O:11])[NH:10][C:5]=2[CH:4]=1.[CH2:17]([NH:19][C:20](=[O:33])[C:21]1[CH:26]=[CH:25][C:24]([N:27]2[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]2)=[CH:23][CH:22]=1)[CH3:18].[I-].C(C[P+](C)(C)C)#N.C(N(C(C)C)C(C)C)C>C(#N)CC>[CH2:17]([NH:19][C:20](=[O:33])[C:21]1[CH:22]=[CH:23][C:24]([N:27]2[CH2:28][CH2:29][N:30]([CH2:2][C:3]3[CH:16]=[N:15][C:6]4[C:7]5[N:8]([CH:12]=[CH:13][CH:14]=5)[C:9](=[O:11])[NH:10][C:5]=4[CH:4]=3)[CH2:31][CH2:32]2)=[CH:25][CH:26]=1)[CH3:18]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 10514344(Cyanomethyl)trimethylphosphanium iodideHCID 28749590N-ethyl-4-(piperazin-1-yl)benzamideHCID 509163263-(hydroxymethyl)pyrido[2,3-e]pyrrolo[1,2-c]pyrimidin-6(5H)-one

Product 1

HCID 50916327N-ethyl-4-(4-((6-oxo-5,6-dihydropyrido[2,3-e]pyrrolo[1,2-c]pyrimidin-3-yl)methyl)piperazin-1-yl)benzamideYield 59.5%

Reagents, catalysts & solvents 1

HCID 7854PropionitrileSolvent

Conditions

Temperature
95 °C

Procedure

To a suspension of 3-(hydroxymethyl)pyrido[2,3-e]pyrrolo[1,2-c]pyrimidin-6(5H)-one (50.00 mg, 0.232 mmol), N-ethyl-4-(piperazin-1-yl)benzamide (67.8 mg, 0.290 mmol) and (cyanomethyl)trimethylphosphonium iodide (90 mg, 0.372 mmol) in propiononitrile (Volume: 1.0 mL) was added N-ethyl-N-isopropylpropan-2-amine (0.202 mL, 1.162 mmol) at 23° C. The reaction was stirred at 95° C. for 3 hr. The suspension was cooled to 23° C., filtered, rinsed with ACN (3×2 mL) and dried in vacuo to provide N-ethyl-4-(4-((6-oxo-5,6-dihydropyrido[2,3-e]pyrrolo[1,2-c]pyrimidin-3-yl)methyl)piperazin-1-yl)benzamide (0.0595 g, 0.138 mmol, 59.5% yield) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.09 (t, J=7.20 Hz, 3 H) 2.51-2.60 (m, 4 H) 3.18-3.31 (m, 6 H) 3.62 (s, 2 H) 6.71-6.77 (m, 1 H) 6.94 (m, J=9.09 Hz, 2H) 7.08 (dd, J=3.54, 1.52 Hz, 1 H) 7.58 (d, J=1.77 Hz, 1 H) 7.68 (dd, J=3.03, 1.52 Hz, 1 H) 7.71 (m, J=8.84 Hz, 2 H) 8.17 (t, J=5.56 Hz, 1 H) 8.36 (d, J=1.77 Hz, 1 H) 11.62 (br. s., 1H). ESI-MS: m/z 431.4 (M+H)+. mp=251.7-259.6° C.

Workup

  1. temperatureThe suspension was cooled to 23° C.
  2. filtrationfiltered
  3. washrinsed with ACN (3×2 mL)
  4. customdried in vacuo

Sources & evidence

ORD record
ord-46f986ceb8ee446980a4527d72f140df
Source dataset
uspto-grants-2013_09
Patent number
US08541417B2

Linked notes

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