Phthalimide, N-(2-formylethyl)- → Ethyl 3-{[3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propyl]amino}-5-[(4-fluorophenyl)methyl]-2-pyridinecarboxylate

HRID 2364219Notes

Reaction equation

HRID 2364219 reaction equation
[NH2:1][C:2]1[C:3]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[N:4][CH:5]=[C:6]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([F:15])=[CH:11][CH:10]=2)[CH:7]=1.[O:21]=[C:22]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[C:24](=[O:31])[N:23]1[CH2:32][CH2:33][CH:34]=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(O)(=O)C>[O:21]=[C:22]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[C:24](=[O:31])[N:23]1[CH2:32][CH2:33][CH2:34][NH:1][C:2]1[C:3]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[N:4][CH:5]=[C:6]([CH2:8][C:9]2[CH:10]=[CH:11][C:12]([F:15])=[CH:13][CH:14]=2)[CH:7]=1

Participants

5

Reactant 3

HCID 75525Phthalimide, N-(2-formylethyl)-HCID 5049666Sodium triacetoxyborohydrideHCID 42637772Ethyl 3-amino-5-(4-fluorobenzyl)picolinate

Product 1

HCID 69482136Ethyl 3-{[3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propyl]amino}-5-[(4-fluorophenyl)methyl]-2-pyridinecarboxylate

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A solution of ethyl 3-amino-5-(4-fluorobenzyl)-2-pyridinecarboxylate (1.00 g, 3.65 mmol) and 3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propanal (0.929 g, 4.57 mmol) under nitrogen in glacial acetic acid (10 mL) was treated with sodium triacetoxyborohydride (1.55 g, 7.31 mmol) at ambient temperature. After stirring for 20 min., the reaction was evaporated in vacuo and the residue was partitioned between EtOAc and 5% w/v aq. K2CO3. After separating the layers, the aqueous phase was diluted with sat. aq. NaCl and back-extracted with EtOAc. The combined organic layers were washed with sat. aq. NaCl, dried over MgSO4, filtered and evaporated in vacuo. The residue was dissolved in warm Et2O leaving a small residue of insolubles. The Et2O was decanted and evaporated to approximately half volume where precipitation occurred. The product was collected by filtration and dried under high vacuum: 1H NMR (d6-DMSO) δ 7.78-7.86 (4H, m), 7.73 (1H, s), 7.65 (1H, t, J=7 Hz), 7.25-7.30 (2H, m), 7.06-7.12 (3H, m), 4.18 (2H, q, J=7 Hz), 3.90 (2H, s), 3.65 (2H, t, J=6 Hz), 3.24 (2H, q, J=5 Hz), 1.80-1.89 (2H, m), 1.24 (3H, t, 7 Hz); ES+ MS: 462 (M+H+).

Workup

  1. customthe reaction was evaporated in vacuo
  2. customthe residue was partitioned between EtOAc and 5%
  3. customAfter separating the layers
  4. additionthe aqueous phase was diluted with sat. aq. NaCl
  5. extractionback-extracted with EtOAc
  6. washThe combined organic layers were washed with sat. aq. NaCl
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. customevaporated in vacuo
  10. dissolutionThe residue was dissolved in warm Et2O leaving a small residue of insolubles
  11. customThe Et2O was decanted
  12. customevaporated to approximately half volume where precipitation
  13. filtrationThe product was collected by filtration
  14. customdried under high vacuum

Sources & evidence

ORD record
ord-2fac1c4ba7684fbcb35adeb98627e7c9
Source dataset
uspto-grants-2014_04
Patent number
US08691991B2

Reaction notes

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