4-Methylmorpholine → HCID 49841101, compound

HRID 1968286Notes

Reaction equation

HRID 1968286 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=C2N=NN(O)C2=CC=1.O.CCN=C=[N:37][CH2:38][CH2:39][CH2:40][N:41]([CH3:43])C.Cl.Cl.N1CC(C#N)C1.CN1CCOCC1>CN(C=O)C>[CH3:21][C:2]([CH3:1])([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]([N:41]1[CH2:40][CH:39]([C:38]#[N:37])[CH2:43]1)=[O:5]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 45072465Azetidine-3-carbonitrile hydrochlorideHCID 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 49841101HCID 49841101, compoundYield 39%

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 (80 mg, 0.278 mmol), HOBt hydrate (51.2 mg, 0.334 mmol), and EDC hydrochloride (80 mg, 0.418 mmol) were combined in DMF (2 mL). Azetidine-3-carbonitrile hydrochloride (49.5 mg, 0.418 mmol) and 4-methylmorpholine (0.124 mL, 1.114 mmol) were added, and the reaction mixture was stirred at room temperature for 2 h. The product was purified by preparative HPLC (10-50% AcCN/H2O with 0.035% TFA), concentrated in vacuo, and purified by flash column chromatography (8% MeOH/DCM) to afford the title compound (38 mg, 39%). 1H NMR (500 MHz, CD3OD) δ 1.17 (s, 9H), 3.58-3.72 (m, 1H), 4.13-4.65 (m, 4H), 5.35-5.45 (m, 3H), 7.28-7.38 (m, 1H), 7.95 (d, J=15.5 Hz, 1H), 8.33-8.40 (m, 1H). [M+H] calc'd for C19H21N5O2, 352; found, 352.

Workup

  1. customThe product was purified by preparative HPLC (10-50% AcCN/H2O with 0.035% TFA)
  2. concentrationconcentrated in vacuo
  3. custompurified by flash column chromatography (8% MeOH/DCM)

Sources & evidence

ORD record
ord-a053516da4c24016a78ffdfa02c637be
Source dataset
uspto-grants-2013_04
Patent number
US08420816B2

Reaction notes

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