1,2-Dichloroethane → (R)-3-methyl-1-(3-methyl-2-(3-oxopyrrolo[4,3,2-de][2,6]naphthyridin-4(1H,3H,5H)-yl)butanoyl)azetidine-3-carbonitrile

HRID 1627176Notes

Reaction equation

HRID 1627176 reaction equation
[CH3:1][CH:2]([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]([OH:6])=O.[C:21]([C:23]1([CH3:27])[CH2:26][NH:25][CH2:24]1)#[N:22].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl>CN(C)C1C=CN=CC=1.CN(C=O)C>[CH3:27][C:23]1([C:21]#[N:22])[CH2:26][N:25]([C:4](=[O:6])[C@H:3]([N:7]2[C:16](=[O:17])[C:15]3=[CH:18][NH:19][C:13]4[C:14]3=[C:9]([CH:10]=[CH:11][N:12]=4)[CH2:8]2)[CH:2]([CH3:20])[CH3:1])[CH2:24]1

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 552994843-Methylazetidine-3-carbonitrileHCID 67224069(R)-3-Methyl-2-(3-oxopyrrolo [4,3,2-de][2,6]naphthyridin-4(1H,3H,5H)-yl)butanoic acid

Product 1

HCID 49842491(R)-3-methyl-1-(3-methyl-2-(3-oxopyrrolo[4,3,2-de][2,6]naphthyridin-4(1H,3H,5H)-yl)butanoyl)azetidine-3-carbonitrileYield 30.6%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

To an 8 mL scintillation vial equipped for stirring was added (R)-3-methyl-2-(3-oxopyrrolo[4,3,2-de][2,6]naphthyridin-4(1H,3H,5H)-yl)butanoic acid (80 mg, 0.293 mmol). DMF (0.5 mL), 3-cyano-3-methylazetidine (85 mg, 0.439 mmol), HOBt (67.2 mg, 0.439 mmol), EDC (84 mg, 0.439 mmol) and N,N-dimethylpyridin-4-amine (53.6 mg, 0.439 mmol) were added and the solution was stirred at 25° C. for 4 h. The fractions were collected and lyophilized to afford the title compound as a white solid (31.5 mg, 30.6%). 1H NMR (400 MHz, DMSO-d6) δ 0.78 (dd, J=6.82, 3.28 Hz, 3 H) 0.96 (dd, J=8.59, 6.32 Hz, 3 H) 1.44-1.68 (m, 3 H) 2.26-2.44 (m, 1 H) 3.84 (dd, J=9.47, 5.18 Hz, 1 H) 3.99-4.14 (m, 1 H) 4.21 (dd, J=9.47, 5.68 Hz, 1 H) 4.34-4.65 (m, 1 H) 4.85 (dd, J=19.45, 5.56 Hz, 1 H) 4.96-5.11 (m, 2 H) 7.08 (d, J=5.05 Hz, 1H) 7.86 (d, J=4.04 Hz, 1 H) 8.26 (dd, J=4.80, 3.28 Hz, 1 H) 12.22 (br. s., 1 H). [M+H] calc'd for C19H21N5O2, 352; found, 352.5.

Workup

  1. customTo an 8 mL scintillation vial equipped
  2. stirringthe solution was stirred at 25° C. for 4 h
  3. customThe fractions were collected

Sources & evidence

ORD record
ord-e1c7be6aeaf24fdd8e1438ac49b4f8e2
Source dataset
uspto-grants-2014_07
Patent number
US08785429B2

Reaction notes

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