4-Methylmorpholine → (2R)-N-(1-cyanoethyl)-2-(6-fluoro-3-oxopyrrolo[4,3,2-de][2,6]naphthyridin-4(1H,3H,5H)-yl)-3-methylbutanamide

HRID 1968275Notes

Reaction equation

HRID 1968275 reaction equation
[F:1][C:2]1[C:11]2[CH2:10][N:9]([C@H:12]([CH:16]([CH3:18])[CH3:17])[C:13]([OH:15])=O)[C:8](=[O:19])[C:7]3=[CH:20][NH:21][C:5]([C:6]=23)=[N:4][CH:3]=1.C1C=[C:26]2[N:28]=N[N:30](O)[C:25]2=[CH:24]C=1.O.CCN=C=NCCCN(C)C.Cl.Cl.NC(C)C#N.CN1CCOCC1>CN(C=O)C>[C:26]([CH:25]([NH:30][C:13](=[O:15])[C@H:12]([N:9]1[C:8](=[O:19])[C:7]2=[CH:20][NH:21][C:5]3[C:6]2=[C:11]([C:2]([F:1])=[CH:3][N:4]=3)[CH2:10]1)[CH:16]([CH3:18])[CH3:17])[CH3:24])#[N:28]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 127828772-Aminopropanenitrile hydrochlorideHCID 57389932HCID 57389932, compound

Product 1

HCID 49842826(2R)-N-(1-cyanoethyl)-2-(6-fluoro-3-oxopyrrolo[4,3,2-de][2,6]naphthyridin-4(1H,3H,5H)-yl)-3-methylbutanamideYield 62.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(R)-2-(6-Fluoro-3-oxopyrrolo[4,3,2-de][2,6]naphthyridin-4(1H,3H,5H)-yl)-3-methylbutanoic acid (15 mg, 0.051 mmol), HOBt hydrate (9.46 mg, 0.062 mmol), and EDC hydrochloride (14.81 mg, 0.077 mmol) were combined in DMF (2 mL). 2-Aminopropanenitrile hydrochloride (8.23 mg, 0.077 mmol) and 4-methylmorpholine (0.023 mL, 0.206 mmol) were added and the reaction mixture was stirred at room temperature for 2 h. Following reaction, the product was purified by preparative HPLC (10-55% AcCN/H2O with 0.035% TFA), concentrated in vacuo, and lyophilized to afford the title compound as a white solid (11 mg, 62%). 1H NMR (500 MHz, DMSO-d6) δ 1.20-1.26 (m, 3H), 1.32-1.39 (m, 3H), 1.77-1.82 (m, 3H), 2.76-2.84 (m, 1H), 5.06-5.22 (m, 1H), 5.36-5.44 (m, 2H), 5.77 (dd, J=19.0, 2.0 Hz, 1H), 8.38 (dd, J=10.5, 2.0 Hz, 1H), 8.65 (t, J=3.0 Hz, 1H), 9.47 (d, J=2.0 Hz, 1H), 12.78 (br d, J=7.5 Hz, 1H). [M+H] calc'd for C17H18FN5O2, 344; found, 344.

Workup

  1. customreaction
  2. customthe product was purified by preparative HPLC (10-55% AcCN/H2O with 0.035% TFA)
  3. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-caab80a1e87448248668f94b2dfe0893
Source dataset
uspto-grants-2013_04
Patent number
US08420816B2

Reaction notes

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