Sodium Hydroxide → HCID 71711819, compound

HRID 470942Notes

Reaction equation

HRID 470942 reaction equation
[CH2:1]([N:8]1[CH2:17][CH2:16][C:15]2[N:14]=[C:13]([CH3:18])[C:12]([CH:19]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])[C:20]([O:22]C)=[O:21])=[C:11]([C:29]3[CH:34]=[CH:33][C:32]([CH3:35])=[CH:31][CH:30]=3)[C:10]=2[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Na+]>O1CCOCC1>[CH2:1]([N:8]1[CH2:17][CH2:16][C:15]2[N:14]=[C:13]([CH3:18])[C:12]([CH:19]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])[C:20]([OH:22])=[O:21])=[C:11]([C:29]3[CH:30]=[CH:31][C:32]([CH3:35])=[CH:33][CH:34]=3)[C:10]=2[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 86692203HCID 86692203, compound2×

Product 1

HCID 71711819HCID 71711819, compoundYield 65%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of methyl 2-(6-benzyl-2-methyl-4-(p-tolyl)-5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)-2-(tert-butoxy)acetate (intermediate 16) (47.3 mg, 100 mmol) in dioxane (3 ml) was added 1N NaOH (1.0 mL) and the mixture was stirred at 70° C. for 1 h. The mixture was quenched with 1 ml 1N HCl and concentrated. The crude material was purified via preparative LC/MS with the following conditions: Column: Waters XBridge C18, 19×150 mm, 5-μm particles; Guard Column: Waters XBridge C18, 19×10 mm, 5-μm particles; Mobile Phase A: water with 20-mM ammonium acetate; Mobile Phase B: 95:5 methanol:water with 20-mM ammonium acetate; Gradient: 60-100% B over 30 minutes, then a 5-minute hold at 100% B; Flow: 20 mL/min. Fractions containing the desired product were combined and dried via centrifugal evaporation to provide 2-(6-benzyl-2-methyl-4-(p-tolyl)-5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)-2-(tert-butoxy)acetic acid (29.9 mg, 65% yield). 1H NMR (500 MHz, DMSO-d6) δ ppm 7.20-7.35 (m, 7H), 7.17 (d, J=7.63 Hz, 1H), 7.09 (dd, J=1.53, 7.63 Hz, 1H), 4.77 (s, 1H), 3.44-3.58 (m, 2H), 3.30 (br. s., 1H), 2.99 (d, J=15.56 Hz, 1H), 2.81-2.89 (m, 2H), 2.75 (td, J=5.49, 10.99 Hz, 1H), 2.56-2.65 (m, 1H), 2.48 (s, 3H), 2.37 (s, 3H), 0.87 (s, 9H). LCMS (M+H) calcd for C29H35N2O3: 459.26. found: 459.3.

Workup

  1. customThe mixture was quenched with 1 ml 1N HCl
  2. concentrationconcentrated
  3. customThe crude material was purified via preparative LC/MS with the following conditions
  4. waitGradient: 60-100% B over 30 minutes
  5. customa 5-minute hold
  6. additionFractions containing the desired product
  7. customdried via centrifugal evaporation

Sources & evidence

ORD record
ord-37b45b0d0c6841ec904089945fe296fe
Source dataset
uspto-grants-2014_01
Patent number
US08629276B2

Reaction notes

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