Hydrochloric Acid → HCID 60152083, compound

HRID 537535Notes

Reaction equation

HRID 537535 reaction equation
[CH3:1][C:2]([CH3:32])([CH3:31])[CH2:3][CH:4]([C:21]1[CH:30]=[CH:29][C:24]([C:25](OC)=[O:26])=[CH:23][CH:22]=1)[NH:5][C:6]1[CH:7]=[N:8][C:9]([N:12]2[CH:16]=[C:15]([C:17]([F:20])([F:19])[F:18])[N:14]=[CH:13]2)=[CH:10][CH:11]=1.[OH-].[Li+].Cl.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.Cl.[NH2:61][CH2:62][CH2:63][C:64]([O:66]C)=[O:65].C(NC(C)C)(C)C.[Cl-].[NH4+]>O1CCCC1>[CH3:31][C:2]([CH3:1])([CH3:32])[CH2:3][CH:4]([C:21]1[CH:22]=[CH:23][C:24]([C:25]([NH:61][CH2:62][CH2:63][C:64]([OH:66])=[O:65])=[O:26])=[CH:29][CH:30]=1)[NH:5][C:6]1[CH:7]=[N:8][C:9]([N:12]2[CH:16]=[C:15]([C:17]([F:18])([F:20])[F:19])[N:14]=[CH:13]2)=[CH:10][CH:11]=1

Participants

9

Reactant 7

HCID 313Hydrochloric Acid2×HCID 3939Lithium Hydroxide2×HCID 7912DiisopropylamineHCID 25517Ammonium ChlorideHCID 2734767Methyl 3-aminopropanoate hydrochlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 68156585HCID 68156585, compound

Product 1

HCID 60152083HCID 60152083, compoundYield 41%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of methyl 4-(3,3-dimethyl-1-(6-(4-(trifluoromethyl)-1H-imidazol-1-yl)pyridine-3-ylamino)butyl)benzoate (50 mg, 0.11 mmol) in tetrahydrofuran (5 mL) was added 2N lithium hydroxide (5 mL, 10 mmol). The reaction mixture was heated to 70° C. for 12 hours. The mixture was adjusted to pH=2 by addition of 1N aqueous hydrochloric acid and the resulting solution extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered and concentrated. The residue was dissolved in N,N-dimethylformamide (5 mL). O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (70.0 mg, 0.184 mmol) was added and the solution stirred at room temperature for 30 minutes. Methyl 3-aminopropionate hydrochloride (19.3 mg, 0.138 mmol) was added followed by diisopropylamine (47.6 mg, 0.37 mmol). The resulting mixture was stirred at room temperature for 1 hour. Saturated aqueous ammonium chloride was added and the mixture was extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered and concentrated. The residue was dissolved in tetrahydrofuran (4 mL) and 2N Lithium hydroxide (4 mL, 8 mmol) was added. The mixture was stirred at room temperature for 1 hour. 1N Aqueous hydrochloric acid was added to adjust the pH=2 and the solution was extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered and concentrated. Purification by HPLC (column: Boston Analytics Symmetrix ODS-H 150×30 mm, 5 μm; modifier: formic acid 0.225%; gradient: 39 to 59% acetonitrile in water) gave (+/−)-3-(4-(3,3-dimethyl-1-(6-(4-(trifluoromethyl)-1H-imidazol-1-yl)pyridine-3-ylamino)butyl)benzamido) propanoic acid (22.7 mg, 41%). 1H NMR (400 MHz, CD3OD, δ): 8.21 (s, 1H), 8.01 (s, 1H), 7.72 (s, 1H), 7.65 (d, 2H), 7.36 (d, 2H), 7.26 (d, 1H), 6.94 (m, 1H), 4.48-4.45 (m, 1H), 3.51-3.48 (m, 2H), 2.53-2.49 (m, 2H), 1.81-1.75 (m, 1H), 1.58-1.53 (m, 1H), 0.94 (s, 9H). MS (M+1): 504.3.

Workup

  1. extractionthe resulting solution extracted with ethyl acetate
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. dissolutionThe residue was dissolved in N,N-dimethylformamide (5 mL)
  6. stirringThe resulting mixture was stirred at room temperature for 1 hour
  7. extractionthe mixture was extracted with ethyl acetate
  8. dry with materialThe organic layer was dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. dissolutionThe residue was dissolved in tetrahydrofuran (4 mL)
  12. stirringThe mixture was stirred at room temperature for 1 hour
  13. extractionthe solution was extracted with ethyl acetate
  14. dry with materialThe organic layer was dried over sodium sulfate
  15. filtrationfiltered
  16. concentrationconcentrated
  17. customPurification by HPLC (column: Boston Analytics Symmetrix ODS-H 150×30 mm, 5 μm; modifier: formic acid 0.225%; gradient: 39 to 59% acetonitrile in water)

Sources & evidence

ORD record
ord-73f19c42dde54dff8d095c58d7305246
Source dataset
uspto-grants-2014_10
Patent number
US08859591B2

Reaction notes

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