Diisopropylethylamine → (S)-N-methyl-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)benzenesulfonamide

HRID 716358Notes

Reaction equation

HRID 716358 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.[CH3:17][NH:18][S:19]([C:22]1[CH:27]=[CH:26][C:25]([N:28]2[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]2)=[CH:24][CH:23]=1)(=[O:21])=[O:20].[I-].C(C[P+](C)(C)C)#N.C(N(CC)C(C)C)(C)C>C(#N)CC>[CH3:17][NH:18][S:19]([C:22]1[CH:23]=[CH:24][C:25]([N:28]2[CH2:33][CH2:32][N:31]([CH2:2][C:3]3[CH:12]=[N:11][C:10]4[N:9]5[CH2:13][CH2:14][CH2:15][C@H:8]5[C:7](=[O:16])[NH:6][C:5]=4[CH:4]=3)[CH2:30][CH2:29]2)=[CH:26][CH:27]=1)(=[O:20])=[O:21]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 10514344(Cyanomethyl)trimethylphosphanium iodideHCID 23288834N-methyl-4-(piperazin-1-yl)benzene-1-sulfonamideHCID 58324378(S)-3-(hydroxymethyl)-6a,7,8,9-tetrahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-6(5H)-one

Product 1

HCID 46864648(S)-N-methyl-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)benzenesulfonamideYield 52.9%

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), N-methyl-4-(piperazin-1-yl)benzenesulfonamide (116 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, 10-95% ACN in water). The fractions were concentrated in vacuo and the resulting solid was recrystallized from water-methanol (2:1, 6 mL) and dried in vacuum to afford (S)—N-methyl-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)benzenesulfonamide (110 mg, 0.241 mmol, 52.8% yield) as a tan solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.88-2.04 (m, 3H) 2.15-2.27 (m, 1H) 2.38 (d, J=4.80 Hz, 3H) 2.51 (d, J=4.29 Hz, 4H) 3.32 (br. s., 4H) 3.38-3.49 (m, 3H) 3.57-3.69 (m, 1H) 3.97-4.07 (m, 1H) 7.02 (d, J=1.52 Hz, 1H) 7.07 (d, J=9.09 Hz, 2H) 7.15 (q, J=4.72 Hz, 1H) 7.59 (d, J=8.84 Hz, 2H) 7.66 (d, J=1.77 Hz, 1H) 10.48 (s, 1H). [M+H] calc'd for C24H29ClN6O2, 457. found, 457.

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-methanol (2:1, 6 mL)
  7. customdried in vacuum

Sources & evidence

ORD record
ord-eaa32b2a3faf4a72b9f881e12f59a900
Source dataset
uspto-grants-2015_11
Patent number
US09187497B2

Reaction notes

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