Diisopropylethylamine → (S)-4-(4-((6-oxo-6,6a,7,8-tetrahydro-5H-azeto[1,2-a]pyrido[3,2-e]pyrazin-3-yl)methyl)piperazin-1-yl)benzonitrile

HRID 2097886

Reaction equation

HRID 2097886 reaction equation
O[CH2:2][C:3]1[CH:12]=[N:11][C:10]2[N:9]3[CH2:13][CH2:14][C@H:8]3[C:7](=[O:15])[NH:6][C:5]=2[CH:4]=1.[N:16]1([C:22]2[CH:29]=[CH:28][C:25]([C:26]#[N:27])=[CH:24][CH:23]=2)[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]1.[I-].C(C[P+](C)(C)C)#N.C(N(CC)C(C)C)(C)C>C(#N)CC.CO>[O:15]=[C:7]1[NH:6][C:5]2[CH:4]=[C:3]([CH2:2][N:19]3[CH2:18][CH2:17][N:16]([C:22]4[CH:23]=[CH:24][C:25]([C:26]#[N:27])=[CH:28][CH:29]=4)[CH2:21][CH2:20]3)[CH:12]=[N:11][C:10]=2[N:9]2[CH2:13][CH2:14][C@@H:8]12

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 27339954-(Piperazin-1-yl)benzonitrileHCID 10514344(Cyanomethyl)trimethylphosphanium iodideHCID 58324372(S)-3-(hydroxymethyl)-7,8-dihydro-5H-azeto[1,2-a]pyrido[3,2-e]pyrazin-6(6aH)-one

Product 1

HCID 58324460(S)-4-(4-((6-oxo-6,6a,7,8-tetrahydro-5H-azeto[1,2-a]pyrido[3,2-e]pyrazin-3-yl)methyl)piperazin-1-yl)benzonitrileYield 6.25%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 7854PropionitrileSolvent

Conditions

Temperature
90 °C

Procedure

(S)-3-(hydroxymethyl)-7,8-dihydro-5H-azeto[1,2-a]pyrido[3,2-e]pyrazin-6(6aH)-one (103 mg, 0.5 mmol), 4-(piperazin-1-yl)benzonitrile (108 mg, 0.575 mmol), (cyanomethyl)trimethylphosphonium iodide (207 mg, 0.850 mmol) and N,N-diisopropylethylamine (0.437 ml, 2.500 mmol) were suspended in Propiononitrile (Volume: 1.502 ml) and heated in a closed vial at 90° C. for 23 h. The reaction mixture was cooled, diluted with MeOH (2 mL) and purified using preparative HPLC (basic phase). The fractions containing product were concentrated in vacuo and crystallized from water-methanol (3 mL, ˜5:1) The precipitate was filtered and dried in vacuum to afford (S)-4-(4-((6-oxo-6,6a,7,8-tetrahydro-5H-azeto[1,2-a]pyrido[3,2-e]pyrazin-3-yl)methyl)piperazin-1-yl)benzonitrile (11.7 mg, 0.031 mmol, 6.25% yield) as a light brown solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.37-2.47 (m, 4 H) 2.68-2.80 (m, 1 H) 2.94 (tt, J=10.67, 7.26 Hz, 1 H) 3.30 (d, J=4.80 Hz, 4 H) 3.36 (s, 2 H) 3.87-4.00 (m, 1 H) 4.21 (q, J=7.66 Hz, 1 H) 4.93 (t, 1 H) 6.98 (d, J=1.77 Hz, 1 H) 7.00 (d, J=9.09 Hz, 2 H) 7.57 (d, J=9.09 Hz, 2 H) 7.65 (d, J=1.77 Hz, 1 H) 10.34 (s, 1 H). [M+H] calc'd for C21H22N6O, 374; found, 374.

Workup

  1. temperatureThe reaction mixture was cooled
  2. custompurified
  3. additionThe fractions containing product
  4. concentrationwere concentrated in vacuo
  5. customcrystallized from water-methanol (3 mL, ˜5:1) The precipitate
  6. filtrationwas filtered
  7. customdried in vacuum

Sources & evidence

ORD record
ord-bcc7cf61f87a4aea9725b7069a3919e4
Source dataset
uspto-grants-2013_05
Patent number
US08450323B2

Linked notes

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