Diisopropylethylamine → 2-(2a-Methyl-4-oxo-2a,3,4,5-tetrahydropyrrolo[4,3,2-de]quinolin-1(2H)-yl)-N-(2'-oxo-1',2',5,7-tetrahydrospiro[cyclopenta[c]pyridine-6,3'-pyrrolo[2,3-b]pyridin]-3-yl)acetamide

HRID 1696421Notes

Reaction equation

HRID 1696421 reaction equation
[O:1]=[C:2]1[CH2:11][CH:10]2[CH2:12][N:13]([CH2:14][C:15]([O-:17])=O)[C:8]3[C:9]2=[C:4]([CH:5]=[CH:6][CH:7]=3)[NH:3]1.[Li+].[NH2:19][C:20]1[N:25]=[CH:24][C:23]2[CH2:26][C:27]3([CH2:37][C:22]=2[CH:21]=1)[C:35]1[C:30](=[N:31][CH:32]=[CH:33][CH:34]=1)[NH:29][C:28]3=[O:36].[CH2:38]1CN(C(Cl)=[N+]2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>C1COCC1>[CH3:38][C:10]12[CH2:12][N:13]([CH2:14][C:15]([NH:19][C:20]3[N:25]=[CH:24][C:23]4[CH2:26][C:27]5([CH2:37][C:22]=4[CH:21]=3)[C:35]3[C:30](=[N:31][CH:32]=[CH:33][CH:34]=3)[NH:29][C:28]5=[O:36])=[O:17])[C:8]3[C:9]1=[C:4]([CH:5]=[CH:6][CH:7]=3)[NH:3][C:2](=[O:1])[CH2:11]2

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 27366521-(Chloro-1-pyrrolidinylmethylene)pyrrolidinium HexafluorophosphateHCID 57974077(+/-)-3-amino-5,7-dihydrospiro[cyclopenta[c]pyridine-6,3'-pyrrolo[2,3-b]pyridin]-2'(1'H)-one2×HCID 66636292Lithium (4-oxo-2a,3,4,5-tetrahydropyrrolo[4,3,2-de]quinolin-1(2H)-yl)acetate

Product 1

HCID 251276752-(2a-Methyl-4-oxo-2a,3,4,5-tetrahydropyrrolo[4,3,2-de]quinolin-1(2H)-yl)-N-(2'-oxo-1',2',5,7-tetrahydrospiro[cyclopenta[c]pyridine-6,3'-pyrrolo[2,3-b]pyridin]-3-yl)acetamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of lithium (4-oxo-2a,3,4,5-tetrahydropyrrolo[4,3,2-de]quinolin-1(2H)-yl)acetate, enantiomer B (53 mg, 0.23 mmol, described in Intermediate 12), (±)-3-amino-5,7-dihydrospiro[cyclopenta[c]pyridine-6,3′-pyrrolo[2,3-b]pyridin]-2′(1′H)-one (71 mg, 0.28 mmol, described in Intermediate 3), 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-4ff2b73786724f93b6906ab4a3eba500
Source dataset
uspto-grants-2012_04
Patent number
US08163752B2

Reaction notes

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