Hydrochloric Acid → glucagon receptor antagonists-4

HRID 1892746Notes

Reaction equation

HRID 1892746 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([CH:25]=[C:26]([CH3:37])[C:27]=1[N:28]1[CH:32]=[C:31]([C:33]([F:36])([F:35])[F:34])[CH:30]=[N:29]1)[O:5][C@H:6]([C:10]1[CH:24]=[CH:23][C:13]([C:14]([NH:16][CH2:17][CH2:18][C:19]([O:21]C)=[O:20])=[O:15])=[CH:12][CH:11]=1)[CH2:7][CH2:8][CH3:9].CO.[OH-].[Na+].Cl>O>[CH3:1][C:2]1[CH:3]=[C:4]([CH:25]=[C:26]([CH3:37])[C:27]=1[N:28]1[CH:32]=[C:31]([C:33]([F:35])([F:34])[F:36])[CH:30]=[N:29]1)[O:5][C@H:6]([C:10]1[CH:11]=[CH:12][C:13]([C:14]([NH:16][CH2:17][CH2:18][C:19]([OH:21])=[O:20])=[O:15])=[CH:23][CH:24]=1)[CH2:7][CH2:8][CH3:9]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 14798Sodium HydroxideHCID 68157536HCID 68157536, compound

Product 1

HCID 60151939glucagon receptor antagonists-4Yield 80%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
30 °C

Procedure

To the solution from step 5 was added methanol (40 mL), water (54 mL) and sodium hydroxide (4.34 g, 108 mmol). The reaction was stirred 1 h at 30° C. The solution was acidified with conc. HCl (9.33 mL) and the aq. phase split. The organic solution was washed with 1 N HCl (40 mL). The organic phase was concentrated and the residue taken up in acetonitrile (300 mL). The solution was cooled to 0° C. and stirred 5 h. The solid product was filtered and washed with cold acetonitrile, giving the desired compound as a white solid (14.6 g, 80% yield). 1H NMR (400 MHz, CDCl3) δ: 7.88 (s, 1H), 7.72 (d, J=8.3 Hz, 2H), 7.65 (s, 1H), 7.38 (d, J=8.3 Hz, 2H), 6.89 (t, J=6.2 Hz, 1H), 6.55 (s, 2H), 5.15 (dd, J=7.8, 4.6 Hz, 1H), 3.68 (q, J=6.2 Hz, 2H), 2.65 (t, J=6.2 Hz, 2H), 1.95 (m, 1H), 1.86 (s, 6H), 1.78 (m, 1H), 1.55-1.38 (m, 2H), 0.94 (t, J=7.4 Hz, 3H). The final compound was recrystallized from acetonitrile (5 vol). The compound was heated to 80° C. and then cooled to 0° C. to provide a purity of 99.01%.

Workup

  1. customthe aq. phase split
  2. washThe organic solution was washed with 1 N HCl (40 mL)
  3. concentrationThe organic phase was concentrated
  4. temperatureThe solution was cooled to 0° C.
  5. stirringstirred 5 h
  6. filtrationThe solid product was filtered
  7. washwashed with cold acetonitrile

Sources & evidence

ORD record
ord-035924d0e4f140c38a6ffbd312cd19bb
Source dataset
uspto-grants-2013_08
Patent number
US08507533B2

Reaction notes

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