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

HRID 1627169Notes

Reaction equation

HRID 1627169 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.Cl.[CH:23]1([CH2:26][O:27][NH2:28])[CH2:25][CH2:24]1.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl>CN(C)C1C=CN=CC=1.CN(C=O)C>[CH:23]1([CH2:26][O:27][NH:28][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]([CH3:18])[CH3:17])[CH2:25][CH2:24]1

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 11557279O-(cyclopropylmethyl)hydroxylamine hydrochlorideHCID 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 49842487(R)-N-(cyclopropylmethoxy)-2-(6-fluoro-3-oxopyrrolo[4,3,2-de][2,6]naphthyridin-4(1H,3H,5H)-yl)-3-methylbutanamideYield 27.2%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

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), O-(cyclopropylmethyl)hydroxylamine hydrochloride (6.4 mg, 0.051 mmol), 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 (5 mg, 23%). 1H NMR (400 MHz, CD3OD) δ 0.16-0.24 (m, 2 H) 0.39-0.55 (m, 2 H) 0.93 (d, J=6.57 Hz, 3 H) 1.05 (d, J=6.32 Hz, 3 H) 1.06-1.15 (m, 1 H) 2.53 (dt, J=11.24, 6.51 Hz, 1 H) 3.55-3.73 (m, 2 H) 4.94 (d, J=11.37 Hz, 1 H) 5.07 (d, J=19.20 Hz, 1 H) 5.46 (d, J=18.44 Hz, 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-71545c1cee3a443c880f50c450a47848
Source dataset
uspto-grants-2014_07
Patent number
US08785429B2

Reaction notes

Loading…