Cyanoacetic acid → 3-(4-{3-[7-(1-methyl-cyclohexanecarbonyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-phenyl}-piperazin-1-yl)-3-oxo-propionitrile

HRID 1677482Notes

Reaction equation

HRID 1677482 reaction equation
[CH3:1][C:2]1([C:8]([C:10]2[C:18]3[C:13](=[N:14][CH:15]=[C:16]([C:19]4[CH:24]=[CH:23][CH:22]=[C:21]([N:25]5[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]5)[CH:20]=4)[N:17]=3)[NH:12][CH:11]=2)=[O:9])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1.N1(O)C2C=CC=CC=2N=N1.[C:41]([CH2:43][C:44](O)=[O:45])#[N:42].Cl.CN(C)CCCN=C=NCC>C(Cl)Cl>[CH3:1][C:2]1([C:8]([C:10]2[C:18]3[C:13](=[N:14][CH:15]=[C:16]([C:19]4[CH:20]=[C:21]([N:25]5[CH2:30][CH2:29][N:28]([C:44](=[O:45])[CH2:43][C:41]#[N:42])[CH2:27][CH2:26]5)[CH:22]=[CH:23][CH:24]=4)[N:17]=3)[NH:12][CH:11]=2)=[O:9])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1

Participants

6

Reactant 4

HCID 9740Cyanoacetic acidHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 59540704(1-methyl-cyclohexyl)-[2-(3-piperazin-1-yl-phenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-methanone

Product 1

HCID 595408163-(4-{3-[7-(1-methyl-cyclohexanecarbonyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-phenyl}-piperazin-1-yl)-3-oxo-propionitrileYield 56.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of (1-methyl-cyclohexyl)-[2-(3-piperazin-1-yl-phenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-methanone (130 mg, 0.32 mmol), benzotriazol-1-ol (52 mg, 0.38 mmol), cyano-acetic acid (74 mg, 0.39 mmol), and 3-(3-dimethylaminopropyl)-1-ethylcarbodiimide hydrochloride (74 mg, 0.39 mmol), in DCM (35 ml), was treated with TEA (0.13 ml, 0.97 mmol). After stirring at room temperature for 16 hours, the reaction mixture was partitioned between DCM and water. The organic layers were collected, dried over MgSO4, filtered, and concentrated. Trituration of the resulting solid with 1:1 Et2O/Hex provided 85 mg (56%) of 3-(4-{3-[7-(1-methyl-cyclohexanecarbonyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-phenyl}-piperazin-1-yl)-3-oxo-propionitrile as an off white solid. MP 214-216° C., M+H=471.

Workup

  1. customthe reaction mixture was partitioned between DCM and water
  2. customThe organic layers were collected
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-36be92e3caa44dc7ae7c8f2fa20c97b7
Source dataset
uspto-grants-2011_08
Patent number
US08008298B2

Reaction notes

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