Hydrochloric Acid → HCID 71711894, compound

HRID 470943Notes

Reaction equation

HRID 470943 reaction equation
[C:1]([O:5][CH:6]([C:11]1[C:12]([CH3:36])=[N:13][C:14]2[CH2:15][CH2:16][N:17]([CH2:28][CH2:29][C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[CH2:18][C:19]=2[C:20]=1[C:21]1[CH:26]=[CH:25][C:24]([CH3:27])=[CH:23][CH:22]=1)[C:7]([O:9]C)=[O:8])([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+].Cl>O1CCOCC1>[C:1]([O:5][CH:6]([C:11]1[C:12]([CH3:36])=[N:13][C:14]2[CH2:15][CH2:16][N:17]([CH2:28][CH2:29][C:30]3[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=3)[CH2:18][C:19]=2[C:20]=1[C:21]1[CH:22]=[CH:23][C:24]([CH3:27])=[CH:25][CH:26]=1)[C:7]([OH:9])=[O:8])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 86692207HCID 86692207, compound2×

Product 1

HCID 71711894HCID 71711894, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
75 °C

Procedure

To a solution of methyl 2-(tert-butoxy)-2-(2-methyl-6-phenethyl-4-(p-tolyl)-5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)acetate (intermediate 19) (34.1 mg, 0.070 mmol) in dioxane (1 mL) was added 1N NaOH (0.700 mL) and the reaction was stirred at 75° C. After 1 h, the mixture was cooled to room temperature and neutralized with 0.7 ml 1M HCl then concentrated. The crude material was purified via preparative LC/MS with the following conditions: Column. Waters XBridge C18, 19×200 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 acetonitrile:water with 20-mM ammonium acetate; Gradient: 30-100% B over 12 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 1H NMR (500 MHz, DMSO-d6) δ ppm 7.29-7.38 (m, 2H), 7.21-7.26 (m, 2H), 7.09-7.21 (m, 5H), 4.77 (s, 1H), 3.26 (s, 1H), 2.95 (d, J=14.95 Hz, 1H), 2.88 (br. s., 3H), 2.62-2.76 (m, 3H), 2.58 (d, J=7.02 Hz, 2H), 2.48 (s, 3H), 2.40 (s, 3H), 0.87 (s, 9H). LCMS (M+H) calcd for C30H37N2O3: 473.28. found: 473.1.

Workup

  1. concentrationthen concentrated
  2. customThe crude material was purified via preparative LC/MS with the following conditions
  3. waitGradient: 30-100% B over 12 minutes
  4. customa 5-minute hold
  5. additionFractions containing the desired product
  6. customdried via centrifugal evaporation 1H NMR (500 MHz, DMSO-d6) δ ppm 7.29-7.38 (m, 2H), 7.21-7.26 (m, 2H), 7.09-7.21 (m, 5H), 4.77 (s, 1H), 3.26 (s, 1H), 2.95 (d, J=14.95 Hz, 1H), 2.88 (br. s., 3H), 2.62-2.76 (m, 3H), 2.58 (d, J=7.02 Hz, 2H), 2.48 (s, 3H), 2.40 (s, 3H), 0.87 (s, 9H)

Sources & evidence

ORD record
ord-b42fcb2b276d4dc5b99dccd05977a4a2
Source dataset
uspto-grants-2014_01
Patent number
US08629276B2

Reaction notes

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