1,2-Dichloroethane → (2R)-2-(6-fluoro-3-oxopyrrolo[4,3,2-de][2,6]naphthyridin-4(1H,3H,5H)-yl)-3-methyl-N-(tetrahydrofuran-3-yl)butanamide

HRID 1627165Notes

Reaction equation

HRID 1627165 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.C[NH:23][CH2:24][CH2:25][C:26]#N.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.CN([CH:45]=[O:46])C>CN(C)C1C=CN=CC=1>[F:1][C:2]1[C:11]2[CH2:10][N:9]([C@H:12]([CH:16]([CH3:17])[CH3:18])[C:13]([NH:23][CH:24]3[CH2:25][CH2:26][O:46][CH2:45]3)=[O:15])[C:8](=[O:19])[C:7]3=[CH:20][NH:21][C:5]([C:6]=23)=[N:4][CH:3]=1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 6228DimethylformamideHCID 69656Propanenitrile, 3-(methylamino)-HCID 757711-HydroxybenzotriazoleHCID 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 49842377(2R)-2-(6-fluoro-3-oxopyrrolo[4,3,2-de][2,6]naphthyridin-4(1H,3H,5H)-yl)-3-methyl-N-(tetrahydrofuran-3-yl)butanamideYield 39.3%

Reagents, catalysts & solvents 1

HCID 142844-(Dimethylamino)pyridineCatalyst

Procedure

To an 8 mL scintillation vial equipped for stirring was added (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). DMF (0.5 mL), tetrahydrofuran-3-amine (0.077, 6.7 mg), HOBt (11.83 mg, 0.077 mmol), EDC (14.81 mg, 0.077 mmol) and N,N-dimethylpyridin-4-amine (9.44 mg, 0.077 mmol) were added and the solution was stirred at 25° C. for 4 h. The reaction mixture was purified via preparative mass trigger LC-MS (AcCN/H2O, 20-50%). The fractions were collected and lyophilized to afford the title compound as a white solid (7.3 mg, 39.3%). 1H NMR (400 MHz, CD3OD) δ 0.93 (d, J=6.57 Hz, 3 H) 1.04 (dd, J=6.57, 2.78 Hz, 3 H) 1.74-1.95 (m, 1 H) 2.21 (d, J=7.83 Hz, 1 H) 2.42-2.54 (m, 1 H) 3.50-3.67 (m, 1 H) 3.69-3.97 (m, 3 H) 4.37 (td, J=3.85, 1.89 Hz, 1 H) 4.96-5.12 (m, 2 H) 5.36-5.52 (m, 1 H) 7.86 (s, 1 H) 8.17 (d, J=3.28 Hz, 1 H). [M+H] calc'd for C18H21FN4O3, 361; found, 361.4.

Workup

  1. customTo an 8 mL scintillation vial equipped
  2. stirringthe solution was stirred at 25° C. for 4 h
  3. customThe reaction mixture was purified via preparative mass trigger LC-MS (AcCN/H2O, 20-50%)
  4. customThe fractions were collected

Sources & evidence

ORD record
ord-8415d4bb4ea24af4a86d2cffea2fc2a5
Source dataset
uspto-grants-2014_07
Patent number
US08785429B2

Reaction notes

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