Cyanoacetic acid → HCID 178511173, compound

HRID 1257578Notes

Reaction equation

HRID 1257578 reaction equation
[NH:1]1[CH2:6][CH2:5][CH2:4][C@@H:3]([N:7]2[C:18]3[C:10](=[CH:11][N:12]=[C:13]4[C:17]=3[CH:16]=[CH:15][NH:14]4)[N:9]=[N:8]2)[CH2:2]1.[C:19]([CH2:21][C:22](O)=[O:23])#[N:20].ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>C(Cl)Cl.CN(C)C1C=CN=CC=1>[O:23]=[C:22]([N:1]1[CH2:6][CH2:5][CH2:4][C@@H:3]([N:7]2[C:18]3[C:10](=[CH:11][N:12]=[C:13]4[C:17]=3[CH:16]=[CH:15][NH:14]4)[N:9]=[N:8]2)[CH2:2]1)[CH2:21][C:19]#[N:20]

Participants

7

Reactant 4

HCID 9740Cyanoacetic acidHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 178419837HCID 178419837, compound

Product 1

HCID 178511173HCID 178511173, compoundYield 92%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of (R)-1-piperidin-3-yl-1,6-dihydro-1,2,3,5,6-pentaaza-as-indacene (72 mg, 297 μmol) in DCM (15 ml) at 0° C., cyanoacetic acid (30.0 mg, 357 μmol), N-hydroxybenzotriazole (56.0 mg, 416 μmol), 4-(dimethylamino)pyridine (58.0 mg, 475 μmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (91.0 mg, 475 μmol) were added. The mixture was then stirred at ambient temperature for 18 hours. The crude reaction mixture was purified by column chromatography on silica gel (gradient: 0 to 6% methanol in DCM) affording 82 mg (92%) of 3-oxo-3-[(R)-3-(6H-1,2,3,5,6-pentaaza-as-indacen-1-yl)-piperidin-1-yl]propionitrile. LCMS (Method A, ESI): RT=2.73 min, m+H=310.1; 1H NMR (400 MHz, DMSO-d6) δ: 12.38 (s, 1H), 9.02 (s, 1H), 7.64-7.59 (m, 1H), 7.12 (m, 1H), 5.28-4.96 (m, 1H), 4.81-4.31 (m, 1H), 4.20-3.70 (m, 3H), 3.36-2.96 (m, 2H), 2.44-1.68 (m, 4H).

Workup

  1. customThe crude reaction mixture
  2. customwas purified by column chromatography on silica gel (gradient: 0 to 6% methanol in DCM)

Sources & evidence

ORD record
ord-9aec1f6076ea4d75a004c5471ee5e2b4
Source dataset
uspto-grants-2013_06
Patent number
US08461328B2

Reaction notes

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