Triethylamine → HCID 10186401, compound

HRID 1016654Notes

Reaction equation

HRID 1016654 reaction equation
O.[OH-].[Li+].[Cl:4][C:5]1[CH:6]=[C:7]2[C:13]([CH2:14][CH2:15][C:16](OC)=[O:17])=[C:12]([C:20]3[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=3)[N:11]([CH3:27])[C:8]2=[N:9][CH:10]=1.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C.Cl.CN(C)CCCN=C=NCC.[C:57]1([CH2:63][C:64]2([OH:70])[CH2:69][CH2:68][NH:67][CH2:66][CH2:65]2)[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=1>CO.O1CCCC1.O>[Cl:4][C:5]1[CH:6]=[C:7]2[C:13]([CH2:14][CH2:15][C:16]([N:67]3[CH2:66][CH2:65][C:64]([CH2:63][C:57]4[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=4)([OH:70])[CH2:69][CH2:68]3)=[O:17])=[C:12]([C:20]3[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=3)[N:11]([CH3:27])[C:8]2=[N:9][CH:10]=1

Participants

10

Reactant 6

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 981524-Benzyl-4-piperidinolHCID 168937Lithium hydroxide, monohydrate2×HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 18407044HCID 18407044, compound

Product 1

HCID 10186401HCID 10186401, compoundYield 83%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

Lithium hydroxide monohydrate (15 mg, 0.34 mmol) was added to a solution of methyl 5-chloro-2-(4-chlorophenyl)-1-methyl-1H-pyrrolo[2,3-b]pyridine-3-propanoate (Description 5, 82 mg, 0.23 mmol) in methanol (15 mL), tetrahydrofuran (5 mL) and water (5 mL) and the mixture was stirred at room temperature overnight. Further lithium hydroxide monohydrate (15 mg, 0.34 mmol) was added and the mixture was stirred at 75° C. for 2 h. The solvent was evaporated under reduced pressure and the residue was dissolved in tetrahydrofuran (25 mL). 1-Hydroxybenzotriazole (549 mg, 1.84 mmol), triethylamine (255 μl, 1.84 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (348 mg, 1.84 mmol) and 4-(phenylmethyl)-4-piperidinol (352 mg, 1.84 mmol) were added and the mixture was stirred at room temperature overnight. The mixture was poured into water and extracted with ethyl acetate. The combined organic fractions were washed with hydrochloric acid (1M), aqueous sodium carbonate (10%) and brine, dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel, eluting with isohexane/EtOAc (50:50), to give the title compound (98 mg, 83%). 1H NMR (360 MHz, CDCl3) δ 8.28 (1H, d, J 2.2 Hz), 7.90 (1H, d, J 2.2 Hz), 7.27-7.48 (2H, m), 7.36-7.26 (5H, m), 7.16-7.14 (2H, m), 4.36 (1H, m), 3.65 (3H, s), 3.36 (1H, m), 3.19 (1H, m), 3.00 (2H, m), 2.86 (1H, m), 2.67 (2H, s), 2.48 (2H, t, J 7.7 Hz), 1.46 (2H, m), 1.39 (1H, m), and 1.22 (1H, m). m/z (ES+) 522, 524 (M+1).

Workup

  1. stirringthe mixture was stirred at 75° C. for 2 h
  2. customThe solvent was evaporated under reduced pressure
  3. dissolutionthe residue was dissolved in tetrahydrofuran (25 mL)
  4. stirringthe mixture was stirred at room temperature overnight
  5. extractionextracted with ethyl acetate
  6. washThe combined organic fractions were washed with hydrochloric acid (1M), aqueous sodium carbonate (10%) and brine
  7. dry with materialdried (MgSO4)
  8. customthe solvent was evaporated under reduced pressure
  9. customThe residue was purified by flash column chromatography on silica gel
  10. washeluting with isohexane/EtOAc (50:50)

Sources & evidence

ORD record
ord-7ed4be6d84bb4944b5df810137ad0def
Source dataset
uspto-grants-2002_11
Patent number
US06476045B2

Reaction notes

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