Trimethylaluminum → (R)-3,3-dimethyl-2-(6-methyl-3-oxo-1-tosylpyrrolo[4,3,2-de][2,6]naphthyridin-4(1H,3H,5H)-yl)butanoic acid

HRID 1968291Notes

Reaction equation

HRID 1968291 reaction equation
Cl[C:2]1[C:11]2[CH2:10][N:9]([C@H:12]([C:23]([CH3:26])([CH3:25])[CH3:24])[C:13]([O:15]CC3C=CC=CC=3)=[O:14])[C:8](=[O:27])[C:7]3=[CH:28][N:29]([S:30]([C:33]4[CH:39]=[CH:38][C:36]([CH3:37])=[CH:35][CH:34]=4)(=[O:32])=[O:31])[C:5]([C:6]=23)=[N:4][CH:3]=1.[CH3:40][Al](C)C>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O1CCOCC1>[CH3:25][C:23]([CH3:24])([CH3:26])[C@@H:12]([N:9]1[C:8](=[O:27])[C:7]2=[CH:28][N:29]([S:30]([C:33]3[CH:39]=[CH:38][C:36]([CH3:37])=[CH:35][CH:34]=3)(=[O:31])=[O:32])[C:5]3[C:6]2=[C:11]([C:2]([CH3:40])=[CH:3][N:4]=3)[CH2:10]1)[C:13]([OH:15])=[O:14]

Participants

5

Reactant 2

HCID 16682925TrimethylaluminumHCID 58293527(R)-benzyl 2-(6-chloro-3-oxo-1-tosylpyrrolo[4,3,2-de][2,6]naphthyridin-4(1H,3H,5H)-yl)-3,3-dimethylbutanoate2×

Product 1

HCID 58293488(R)-3,3-dimethyl-2-(6-methyl-3-oxo-1-tosylpyrrolo[4,3,2-de][2,6]naphthyridin-4(1H,3H,5H)-yl)butanoic acidYield 439.1%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

(R)-Benzyl 2-(6-chloro-3-oxo-1-tosylpyrrolo[4,3,2-de][2,6]naphthyridin-4(1H,3H,5H)-yl)-3,3-dimethylbutanoate (10 mg, 0.018 mmol), Pd(Ph3P)4 (10 mg, 0.009 mmol), and dioxane (1 mL) were combined in a 2 mL microwave vial. The mixture was purged with nitrogen, and trimethylaluminum (2.0M/toluene, 0.053 mL, 0.11 mmol) was added. The vial was sealed and the reaction mixture was heated in a Biotage Initiator™ microwave for 1 h at 120° C. The reaction was repeated three times with an increased amount of (R)-benzyl 2-(6-chloro-3-oxo-1-tosylpyrrolo[4,3,2-de][2,6]naphthyridin-4(1H,3H,5H)-yl)-3,3-dimethylbutanoate (30 mg) in each reaction. The reaction mixtures were combined and the resulting mixture was concentrated and purified by preparative HPLC (30-70% AcCN/H2O with 0.035% TFA) to afford the title compound as a yellow oil (36 mg, 44%). 1H NMR (500 MHz, CD3OD) δ 1.21 (s, 9H), 2.30 (s, 3H), 2.36 (s, 3H), 4.94 (s, 1H), 5.07 (d, J=18.6 Hz, 1H), 5.21 (d, J=19.0 Hz, 1H), 7.36 (d, J=8.3 Hz, 2H), 8.04 (d, J=4.9 Hz, 2H), 8.10 (s, 1H), 8.22 (s, 1H). [M+H] calc'd for C23H25N3O5S, 456; found, 456

Workup

  1. additionwas added
  2. customThe vial was sealed
  3. customin each reaction
  4. customThe reaction mixtures
  5. concentrationthe resulting mixture was concentrated
  6. custompurified by preparative HPLC (30-70% AcCN/H2O with 0.035% TFA)

Sources & evidence

ORD record
ord-83e99928f91a44a987d24631448a3fcf
Source dataset
uspto-grants-2013_04
Patent number
US08420816B2

Reaction notes

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