Trimethylaluminum → HCID 58293433, compound

HRID 1968294Notes

Reaction equation

HRID 1968294 reaction equation
Cl[C:2]1[C:11]2[CH2:10][N:9]([C@H:12]([CH:21]([CH3:23])[CH3:22])[C:13]([N:15]3[CH2:18][CH:17]([C:19]#[N:20])[CH2:16]3)=[O:14])[C:8](=[O:24])[C:7]3=[CH:25][NH:26][C:5]([C:6]=23)=[N:4][CH:3]=1.[CH3:27][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>[CH3:22][CH:21]([CH3:23])[C@@H:12]([N:9]1[C:8](=[O:24])[C:7]2=[CH:25][NH:26][C:5]3[C:6]2=[C:11]([C:2]([CH3:27])=[CH:3][N:4]=3)[CH2:10]1)[C:13]([N:15]1[CH2:18][CH:17]([C:19]#[N:20])[CH2:16]1)=[O:14]

Participants

5

Reactant 2

HCID 16682925TrimethylaluminumHCID 49842256HCID 49842256, compound

Product 1

HCID 58293433HCID 58293433, compoundYield 144%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

(R)-1-(2-(6-chloro-3-oxopyrrolo[4,3,2-de][2,6]naphthyridin-4(1H,3H,5H)-yl)-3-methylbutanoyl)azetidine-3-carbonitrile (30 mg, 0.081 mmol), Pd(Ph3P)4 (47 mg, 0.04 mmol), and dioxane (2 mL) were combined in a 5 mL microwave vial. The mixture was purged with nitrogen, and trimethylaluminum (2.0M/toluene, 0.24 mL, 0.48 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 4 times at the same scale. The reaction mixtures were combined, and the resulting mixture was quenched with water (0.5 mL), concentrated, and purified by preparative HPLC (10-30% AcCN/H2O with 0.035% TFA) followed by flash chromatography (5% MeOH/95% DCM) to give the title compound as a light yellow solid (41 mg, 29%). 1H NMR (500 MHz, CD3OD) δ 0.92 (d, J=6.8 Hz, 3H), 1.07 (dd, J=15.9, 6.1 Hz, 3H), 2.42 (d, J=6.35 Hz, 3H), 3.69-3.77 (m, 1H), 4.19-4.22 (m, 1H), 4.32-4.34 (m, 1H), 4.53-4.59 (m, 1H), 4.68-4.72 (m, 1H), 5.20-5.33 (m, 3H), 7.98 (d, J=19.5 Hz, 1H), 8.27 (s, 1H). [M+H] calc'd for C19H21N5O2, 352; found, 352.

Workup

  1. additionwas added
  2. customThe vial was sealed
  3. customThe reaction mixtures
  4. customthe resulting mixture was quenched with water (0.5 mL)
  5. concentrationconcentrated
  6. custompurified by preparative HPLC (10-30% AcCN/H2O with 0.035% TFA)

Sources & evidence

ORD record
ord-13a3552473fe419a91f84b532fd97f3f
Source dataset
uspto-grants-2013_04
Patent number
US08420816B2

Reaction notes

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