Diisopropylethylamine → HCID 46864728, compound

HRID 69741Notes

Reaction equation

HRID 69741 reaction equation
O[CH2:2][C:3]1[CH:12]=[N:11][C:10]2[N:9]3[CH2:13][CH2:14][CH2:15][C@H:8]3[C:7](=[O:16])[NH:6][C:5]=2[CH:4]=1.[Cl:17][C:18]1[CH:19]=[C:20]([CH:27]=[CH:28][C:29]=1[N:30]1[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]1)[C:21]([NH:23][CH:24]([CH3:26])[CH3:25])=[O:22].[I-].C(C[P+](C)(C)C)#N.C(N(CC)C(C)C)(C)C>C(#N)CC>[Cl:17][C:18]1[CH:19]=[C:20]([CH:27]=[CH:28][C:29]=1[N:30]1[CH2:31][CH2:32][N:33]([CH2:2][C:3]2[CH:12]=[N:11][C:10]3[N:9]4[CH2:13][CH2:14][CH2:15][C@H:8]4[C:7](=[O:16])[NH:6][C:5]=3[CH:4]=2)[CH2:34][CH2:35]1)[C:21]([NH:23][CH:24]([CH3:26])[CH3:25])=[O:22]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 10514344(Cyanomethyl)trimethylphosphanium iodideHCID 58324378(S)-3-(hydroxymethyl)-6a,7,8,9-tetrahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-6(5H)-oneHCID 583245013-chloro-N-isopropyl-4-(piperazin-1-yl)benzamide

Product 1

HCID 46864728HCID 46864728, compoundYield 55.5%

Reagents, catalysts & solvents 1

HCID 7854PropionitrileSolvent

Conditions

Temperature
105 °C

Procedure

(S)-3-(hydroxymethyl)-6a,7,8,9-tetrahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-6(5H)-one (100 mg, 0.456 mmol), 3-chloro-N-isopropyl-4-(piperazin-1-yl)benzamide (129 mg, 0.456 mmol), (cyanomethyl)trimethylphosphonium iodide (166 mg, 0.684 mmol) and N,N-diisopropylethylamine (0.398 ml, 2.281 mmol) were suspended in propiononitrile (Volume: 1.370 ml) and heated in a closed vial at 90-120° C. for 4 h. The reaction mixture became a dark brown solution. It was cooled to room temperature, concentrated in vacuo, dissolved in DMSO (2 mL) and purified using HPLC (basic, 25-95% ACN in water, basic). The fractions were concentrated in vacuo and the resulting solid was recrystallized from water-MeOH (2:1, 15 mL) and dried in vacuum to afford (S)-3-chloro-N-isopropyl-4-(4-((6-oxo-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-3-yl)methyl)piperazin-1-yl)benzamide (122.1 mg, 0.253 mmol, 55.4% yield) as a light tan solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.14 (d, J=6.57 Hz, 6 H) 1.84-2.03 (m, 3 H) 2.12-2.25 (m, 1 H) 2.50-2.59 (m, 4 H) 3.02 (br. s., 4 H) 3.35-3.45 (m, 3 H) 3.53-3.64 (m, 1 H) 3.94-4.09 (m, 2 H) 6.98 (d, J=1.52 Hz, 1 H) 7.17 (d, J=8.59 Hz, 1 H) 7.63 (d, J=1.77 Hz, 1 H) 7.77 (dd, J=8.34, 2.02 Hz, 1 H) 7.89 (d, J=2.02 Hz, 1 H) 8.18 (d, J=7.58 Hz, 1 H) 10.45 (s, 1 H). [M+H] calc'd for C25H31ClN6O2, 483; found, 483.

Workup

  1. temperatureIt was cooled to room temperature
  2. concentrationconcentrated in vacuo
  3. dissolutiondissolved in DMSO (2 mL)
  4. custompurified
  5. concentrationThe fractions were concentrated in vacuo
  6. customthe resulting solid was recrystallized from water-MeOH (2:1, 15 mL)
  7. customdried in vacuum

Sources & evidence

ORD record
ord-7c54dc48f492416795956880787b82bf
Source dataset
uspto-grants-2014_09
Patent number
US08822470B2

Reaction notes

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