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

HRID 44330

Reaction equation

HRID 44330 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.[F:17][C:18]1[CH:19]=[C:20]([CH:25]=[CH:26][C:27]=1[N:28]1[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]1)[C:21]([NH:23][CH3:24])=[O:22].[I-].C(C[P+](C)(C)C)#N.C(N(C(C)C)C(C)C)C>C(#N)CC>[F:17][C:18]1[CH:19]=[C:20]([CH:25]=[CH:26][C:27]=1[N:28]1[CH2:29][CH2:30][N:31]([CH2:2][C:3]2[CH:16]=[N:15][C:6]3[C:7]4[N:8]([CH:12]=[CH:13][CH:14]=4)[C:9](=[O:11])[NH:10][C:5]=3[CH:4]=2)[CH2:32][CH2:33]1)[C:21]([NH:23][CH3:24])=[O:22]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 10514344(Cyanomethyl)trimethylphosphanium iodideHCID 509163263-(hydroxymethyl)pyrido[2,3-e]pyrrolo[1,2-c]pyrimidin-6(5H)-oneHCID 583244813-fluoro-N-methyl-4-(piperazin-1-yl)benzamide

Product 1

HCID 509165093-fluoro-N-methyl-4-(4-((6-oxo-5,6-dihydropyrido[2,3-e]pyrrolo[1,2-c]pyrimidin-3-yl)methyl)piperazin-1-yl)benzamideYield 80.2%

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), 3-fluoro-N-methyl-4-(piperazin-1-yl)benzamide (68.9 mg, 0.290 mmol) and (cyanomethyl)trimethylphosphonium iodide (90 mg, 0.372 mmol) in Propiononitrile (Volume: 1.00 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 15 hr. The suspension was cooled to 23° C., concentrated via rotary evaporation, re-constituted in ACN (2.0 mL), stirred for 15 min, filtered, rinsed with ACN (3×1 mL) and dried in vacuo. The crude solid was re-suspended in ACN (2.0 mL), heated to reflux, cooled to 23° C., filtered, rinsed with ACN (3×2.0 mL) to provide 3-fluoro-N-methyl-4-(4-((6-oxo-5,6-dihydropyrido[2,3-e]pyrrolo[1,2-c]pyrimidin-3-yl)methyl)piperazin-1-yl)benzamide (0.081 g, 0.186 mmol, 80.0% yield) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.54-2.63 (m, 4H) 2.75 (d, J=4.55 Hz, 3 H) 3.08-3.17 (m, 4 H) 3.63 (s, 2 H) 6.71-6.75 (m, 1 H) 7.02-7.10 (m, 2 H) 7.53-7.63 (m, 3 H) 7.67 (dd, J=3.03, 1.52 Hz, 1 H) 8.29 (q, J=4.29 Hz, 1 H) 8.33-8.38 (m, 1 H) 11.56 (br. s., 1 H). ESI-MS: m/z 435.4 (M+H)+. mp=288.0-294.5° C.

Workup

  1. temperatureThe suspension was cooled to 23° C.
  2. concentrationconcentrated via rotary evaporation, re-constituted in ACN (2.0 mL)
  3. stirringstirred for 15 min
  4. filtrationfiltered
  5. washrinsed with ACN (3×1 mL)
  6. customdried in vacuo
  7. temperatureheated
  8. temperatureto reflux
  9. temperaturecooled to 23° C.
  10. filtrationfiltered
  11. washrinsed with ACN (3×2.0 mL)

Sources & evidence

ORD record
ord-c569d8be534d48dfa18573ba56d9a550
Source dataset
uspto-grants-2013_09
Patent number
US08541417B2

Linked notes

Loading…