Benzenepropanoic acid → N-(2'-Oxo-1',2',5,7-tetrahydrospiro[cyclopenta[b]pyridine-6,3'-pyrrolo[2,3-b]pyridin]-3-yl)-3-phenylpropanamide

HRID 1097439Notes

Reaction equation

HRID 1097439 reaction equation
[C:1]1([CH2:7][CH2:8][C:9]([OH:11])=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH2:12][C:13]1[CH:14]=[C:15]2[CH2:30][C:20]3([C:28]4[C:23](=[N:24][CH:25]=[CH:26][CH:27]=4)[NH:22][C:21]3=[O:29])[CH2:19][C:16]2=[N:17][CH:18]=1.C1CN(C(Cl)=[N+]2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>C1COCC1>[O:29]=[C:21]1[NH:22][C:23]2=[N:24][CH:25]=[CH:26][CH:27]=[C:28]2[C:20]21[CH2:19][C:16]1=[N:17][CH:18]=[C:13]([NH:12][C:9](=[O:11])[CH2:8][CH2:7][C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[CH:14]=[C:15]1[CH2:30]2

Participants

6

Reactant 4

HCID 107Benzenepropanoic acidHCID 81531DiisopropylethylamineHCID 27366521-(Chloro-1-pyrrolidinylmethylene)pyrrolidinium HexafluorophosphateHCID 57974090HCID 57974090, compound2×

Product 1

HCID 25022586N-(2'-Oxo-1',2',5,7-tetrahydrospiro[cyclopenta[b]pyridine-6,3'-pyrrolo[2,3-b]pyridin]-3-yl)-3-phenylpropanamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 3-phenylpropionic acid (35 mg, 0.23 mmol), (±)-3-amino-5,7-dihydrospiro[cyclopenta[b]pyridine-6,3′-pyrrolo[2,3-b]pyridin]-2′(1′H)-one (71 mg, 0.28 mmol, described in Intermediate 4), N,N,N′,N′-bis(tetramethylene)chloroformamidinium hexafluorophosphate (153 mg, 0.46 mmol), and N,N-diisopropylethylamine (0.20 mL, 1.15 mmol) in THF (2 mL) is stirred at ambient temperature for 18 h. The reaction mixture is purified directly by HPLC using a reversed phase C18 column and eluting with a gradient of H2O:CH3CN:CF3CO2H—90:10:0.1 to 5:95:0.1. The pure, product-containing fractions are combined and made basic with saturated aqueous NaHCO3. The resulting mixture is extracted with EtOAc (3×20 mL), and the combined organic extracts are washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo to provide the title compound.

Workup

  1. customThe reaction mixture is purified directly by HPLC
  2. washeluting with a gradient of H2O
  3. additionThe pure, product-containing fractions
  4. extractionThe resulting mixture is extracted with EtOAc (3×20 mL)
  5. washthe combined organic extracts are washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-19749307d2a54cf4bd65eb0ca12e8e57
Source dataset
uspto-grants-2012_03
Patent number
US08143266B2

Reaction notes

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