Cyanoacetic acid → HCID 136342279, compound

HRID 1854347Notes

Reaction equation

HRID 1854347 reaction equation
Cl.[NH:2]1[CH2:7][CH2:6][CH2:5][C@@H:4]([C:8]2[N:12]3[C:13]4[CH:19]=[CH:18][NH:17][C:14]=4[N:15]=[CH:16][C:11]3=[N:10][N:9]=2)[CH2:3]1.[C:20]([CH2:22][C:23](O)=[O:24])#[N:21].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.CCN(C(C)C)C(C)C>CN(C=O)C>[C:8]1([C@@H:4]2[CH2:5][CH2:6][CH2:7][N:2]([C:23](=[O:24])[CH2:22][C:20]#[N:21])[CH2:3]2)[N:12]2[C:13]3[CH:19]=[CH:18][NH:17][C:14]=3[N:15]=[CH:16][C:11]2=[N:10][N:9]=1

Participants

7

Reactant 5

HCID 9740Cyanoacetic acidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 136349069HCID 136349069, compound

Product 1

HCID 136342279HCID 136342279, compoundYield 63.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a suspension of (R)-1-(piperidin-3-yl)-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazine hydrochloride (0.074 g, 0.265 mmol; Example #I1.1) and 2-cyanoacetic acid (0.034 g, 0.398 mmol) in DMF (3 mL) was added HOBt (0.041 g, 0.265 mmol), EDC.HCl (0.051 g, 0.265 mmol) and DIEA (0.093 mL, 0.531 mmol). The reaction mixture was stirred at ambient temperature for about 16 h. The crude reaction mixture was purified by RP-HPLC (Table 2, Method f). The appropriate fractions were concentrated in vacuo and lyophilized to afford (R)-3-(3-(6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)piperidin-1-yl)-3-oxopropanenitrile as a white solid (0.052 g, 63%): LC/MS (Table 2, Method a) Rt=1.30 min; MS m/z: 310 (M+H)+.

Workup

  1. customThe crude reaction mixture
  2. customwas purified by RP-HPLC (Table 2, Method f)
  3. concentrationThe appropriate fractions were concentrated in vacuo

Sources & evidence

ORD record
ord-0b907239b4ea46ecb05f619fcb7aa564
Source dataset
uspto-grants-2015_02
Patent number
US08962629B2

Reaction notes

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