Diisopropylethylamine → (S)-N-cyclopropyl-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

HRID 716226Notes

Reaction equation

HRID 716226 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.[CH:17]1([NH:20][C:21](=[O:34])[C:22]2[CH:27]=[CH:26][C:25]([N:28]3[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]3)=[CH:24][CH:23]=2)[CH2:19][CH2:18]1.[I-].C(C[P+](C)(C)C)#N.C(N(CC)C(C)C)(C)C>C(#N)CC>[CH:17]1([NH:20][C:21](=[O:34])[C:22]2[CH:23]=[CH:24][C:25]([N:28]3[CH2:29][CH2:30][N:31]([CH2:2][C:3]4[CH:12]=[N:11][C:10]5[N:9]6[CH2:13][CH2:14][CH2:15][C@H:8]6[C:7](=[O:16])[NH:6][C:5]=5[CH:4]=4)[CH2:32][CH2:33]3)=[CH:26][CH:27]=2)[CH2:19][CH2:18]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 10514344(Cyanomethyl)trimethylphosphanium iodideHCID 28749052Benzamide, N-cyclopropyl-4-(1-piperazinyl)-HCID 58324378(S)-3-(hydroxymethyl)-6a,7,8,9-tetrahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-6(5H)-one

Product 1

HCID 46864876(S)-N-cyclopropyl-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

Reagents, catalysts & solvents 1

HCID 7854PropionitrileSolvent

Conditions

Temperature
120 °C

Procedure

(S)-3-(hydroxymethyl)-6a,7,8,9-tetrahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-6(5H)-one (300 mg, 1.368 mmol), N-cyclopropyl-4-(piperazin-1-yl)benzamide (336 mg, 1.368 mmol), (cyanomethyl)trimethylphosphonium iodide (499 mg, 2.053 mmol) and N,N-diisopropylethylamine (1195 μl, 6.84 mmol) were suspended in propionitrile (Volume: 4109 μl) and heated in a closed vial at 120° C. for 2 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 (NH4HCO3 buffered, 20-70% ACN in water). The fractions were concentrated in vacuo and the resulting solid was recrystallized from water-MeOH (1:1, 15 mL), and then from MeOH:EtOH:water (1:1:1, 10 mL), washed with water (3 mL) and dried in vacuum to give a light green solid.

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 (1:1, 15 mL)
  7. washfrom MeOH:EtOH:water (1:1:1, 10 mL), washed with water (3 mL)
  8. customdried in vacuum
  9. customto give a light green solid

Sources & evidence

ORD record
ord-2c05d360fb3c45d7ae0552032ff4a666
Source dataset
uspto-grants-2015_11
Patent number
US09187497B2

Reaction notes

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