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

HRID 44332Notes

Reaction equation

HRID 44332 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:26]=[CH:27][C:28]=1[N:29]1[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]1)[C:21]([NH:23][CH2:24][CH3:25])=[O:22].[I-].C(C[P+](C)(C)C)#N.C(N(C(C)C)C(C)C)C>C(#N)CC>[CH2:24]([NH:23][C:21](=[O:22])[C:20]1[CH:26]=[CH:27][C:28]([N:29]2[CH2:34][CH2:33][N:32]([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][CH2:30]2)=[C:18]([F:17])[CH:19]=1)[CH3:25]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 10514344(Cyanomethyl)trimethylphosphanium iodideHCID 509163263-(hydroxymethyl)pyrido[2,3-e]pyrrolo[1,2-c]pyrimidin-6(5H)-oneHCID 58324414HCID 58324414, compound

Product 1

HCID 50916673N-ethyl-3-fluoro-4-(4-((6-oxo-5,6-dihydropyrido[2,3-e]pyrrolo[1,2-c]pyrimidin-3-yl)methyl)piperazin-1-yl)benzamideYield 100%

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 (47.50 mg, 0.221 mmol), 3-fluoro-N-ethyl-4-(piperazin-1-yl)benzamide (69.3 mg, 0.276 mmol) and (cyanomethyl)trimethylphosphonium iodide (86 mg, 0.353 mmol) in Propiononitrile (Volume: 1.00 mL) was added N-ethyl-N-isopropylpropan-2-amine (0.192 mL, 1.104 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 N-ethyl-3-fluoro-4-(4-((6-oxo-5,6-dihydropyrido[2,3-e]pyrrolo[1,2-c]pyrimidin-3-yl)methyl)piperazin-1-yl)benzamide (0.069 g, 0.221 mmol, 70.1% yield) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.10 (t, J=7.20 Hz, 3 H) 2.54-2.64 (m, 4 H) 3.07-3.17 (m, 4 H) 3.21-3.28 (m, 2 H) 3.63 (s, 2 H) 6.71-6.76 (m, 1 H) 7.01-7.10 (m, 2 H) 7.55-7.64 (m, 3 H) 7.67 (dd, J=3.03, 1.52 Hz, 1 H) 8.32 (t, J=5.43 Hz, 1 H) 8.36 (d, J=1.77 Hz, 1 H) 11.58 (br. s., 1 H). ESI-MS: m/z 449.4 (M+H)+. mp=262.7-267.4° 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-ae19f841f64a4c9b9223f123e453da8f
Source dataset
uspto-grants-2013_09
Patent number
US08541417B2

Reaction notes

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