4-Methylmorpholine → HCID 49841212, compound

HRID 1968287Notes

Reaction equation

HRID 1968287 reaction equation
[CH3:1][C:2]([CH3:21])([CH3:20])[C@@H:3]([N:7]1[C:16](=[O:17])[C:15]2=[CH:18][NH:19][C:13]3[C:14]2=[C:9]([CH:10]=[CH:11][N:12]=3)[CH2:8]1)[C:4](O)=[O:5].C1C=[C:26]2[N:28]=N[N:30](O)[C:25]2=CC=1.O.CCN=C=NCCCN(C)C.Cl.NCC#N.CN1CCOCC1>CN(C=O)C>[C:26]([CH2:25][NH:30][C:4](=[O:5])[C@H:3]([N:7]1[C:16](=[O:17])[C:15]2=[CH:18][NH:19][C:13]3[C:14]2=[C:9]([CH:10]=[CH:11][N:12]=3)[CH2:8]1)[C:2]([CH3:20])([CH3:21])[CH3:1])#[N:28]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 10901AminoacetonitrileHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 58293442Pyrrolo[4,3,2-de][2,6]naphthyridine-4(3H)-acetic acid, α-(1,1-dimethylethyl)-1,5-dihydro-3-oxo-, (αR)-

Product 1

HCID 49841212HCID 49841212, compoundYield 79.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(R)-3,3-Dimethyl-2-(3-oxopyrrolo[4,3,2-de][2,6]naphthyridin-4(1H,3H,5H)-yl)butanoic acid (40.0 mg, 0.139 mmol), HOBt hydrate (25.6 mg, 0.167 mmol), and EDC hydrochloride (40.0 mg, 0.209 mmol) were combined in DMF (2 mL). 2-Aminoacetonitrile (11.71 mg, 0.209 mmol) and 4-methylmorpholine (0.062 mL, 0.557 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 pale yellow solid (36 mg, 59%). 1H NMR (500 MHz, DMSO-d6) δ 1.09 (s, 9H), 4.01-4.12 (m, 2H), 5.13-5.22 (m, 2H), 5.33 (br s, 1H), 7.10 (d, J=4.5 Hz, 1H), 7.87 (s, 1H), 8.26 (d, J=4.5 Hz, 1H), 8.86 (br s, 1H), 12.25 (br s, 1H). [M+H] calc'd for C17H19N5O2, 326; found, 326.

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-0aaf1348173148e5a900d2c8cb5046e7
Source dataset
uspto-grants-2013_04
Patent number
US08420816B2

Reaction notes

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