4-Methylmorpholine → HCID 49841096, compound

HRID 1968277Notes

Reaction equation

HRID 1968277 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=C2N=NN(O)C2=CC=1.O.CCN=C=NCCCN(C)C.Cl.Cl.[S:46]1(=[O:52])(=[O:51])[CH2:50][CH2:49][NH:48][CH2:47]1.CN1CCOCC1>CN(C=O)C>[O:51]=[S:46]1(=[O:52])[CH2:50][CH2:49][N:48]([C:13](=[O:15])[C@H:12]([N:9]2[C:8](=[O:19])[C:7]3=[CH:20][NH:21][C:5]4[C:6]3=[C:11]([C:2]([F:1])=[CH:3][N:4]=4)[CH2:10]2)[CH:16]([CH3:17])[CH3:18])[CH2:47]1

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 18965215HCID 18965215, compoundHCID 57389932(R)-2-(6-fluoro-3-oxopyrrolo[4,3,2-de][2,6]naphthyridin-4(1H,3H,5H)-yl)-3-methylbutanoic acid

Product 1

HCID 49841096HCID 49841096, compoundYield 43.7%

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). Thiazolidine 1,1-dioxide hydrochloride (12.17 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. The product was purified by preparative HPLC (10-45% AcCN/H2O with 0.035% TFA), concentrated in vacuo, and lyophilized to afford the title compound as a white solid (8.8 mg, 43%). 1H NMR (500 MHz, DMSO-d6) δ 0.76-0.81 (m, 3H), 0.95 (d, J=6.5 Hz, 3H), 2.41-2.50 (m, 1H), 3.35-3.45 (m, 2H), 3.80-3.89 (m, 2H), 4.49-4.91 (m, 4H), 5.18-5.42 (m, 1H), 8.01 (d, J=2.5 Hz, 1H), 8.24 (d, J=2.5 Hz, 1H), 12.43 (s, 1H). [M+H] calc'd for C17H19FN4O4S, 395; found, 395.

Workup

  1. customThe product was purified by preparative HPLC (10-45% AcCN/H2O with 0.035% TFA)
  2. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-c5fdd309db5f4c1a9caf9946b9f46a48
Source dataset
uspto-grants-2013_04
Patent number
US08420816B2

Reaction notes

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