1,2-Dichloroethane → 2-(4-Oxo-2a,3,4,5-tetrahydropyrrolo[4,3,2-de]quinolin-1(2H)-yl)-N-(2'-oxo-1,1',2',3-tetrahydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridin]-5-yl)acetamide

HRID 641447Notes

Reaction equation

HRID 641447 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]2[C:17](=[CH:18][CH:19]=1)[CH2:16][C:6]1([C:14]3[C:9](=[N:10][CH:11]=[CH:12][CH:13]=3)[NH:8][C:7]1=[O:15])[CH2:5]2.[O:20]=[C:21]1[CH2:30][CH:29]2[CH2:31][N:32]([CH2:33][C:34]([O-])=[O:35])[C:27]3[C:28]2=[C:23]([CH:24]=[CH:25][CH:26]=3)[NH:22]1.[Li+].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.C(N(CC)C(C)C)(C)C>CN(C=O)C>[O:20]=[C:21]1[CH2:30][CH:29]2[CH2:31][N:32]([CH2:33][C:34]([NH:1][C:2]3[CH:3]=[C:4]4[C:17](=[CH:18][CH:19]=3)[CH2:16][C:6]3([C:14]5[C:9](=[N:10][CH:11]=[CH:12][CH:13]=5)[NH:8][C:7]3=[O:15])[CH2:5]4)=[O:35])[C:27]3[C:28]2=[C:23]([CH:24]=[CH:25][CH:26]=3)[NH:22]1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 591667225-amino-1,3-dihydrospiro[indene-2,3'-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 115544992-(4-Oxo-2a,3,4,5-tetrahydropyrrolo[4,3,2-de]quinolin-1(2H)-yl)-N-(2'-oxo-1,1',2',3-tetrahydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridin]-5-yl)acetamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of (−)-5-amino-1,3-dihydrospiro[indene-2,3′-pyrrolo[2,3-b]pyridin]-2′(1′H)-one (108 mg, 0.431 mmol, described in Intermediate 3), lithium (4-oxo-2a,3,4,5-tetrahydropyrrolo[4,3,2-de]quinolin-1(2H)-yl)acetate, enantiomer B (100 mg, 0.431 mmol, described in Intermediate 12), EDC (107 mg, 0.560 mmol), HOBT (86 mg, 0.560 mmol), and N,N-diisopropylethylamine (0.113 mL, 0.646 mmol) was stirred in DMF (3 mL) at ambient temperature for 18 h. The reaction mixture was 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 were combined and concentrated in vacuo. The residue was added to saturated aqueous NaHCO3 (10 mL) and extracted with EtOAc (3×20 mL). The combined organic extract was dried over Na2SO4, filtered, and concentrated in vacuo to give the title compound. MS: m/z=466 (M+1). HRMS: m/z=466.1913; calculated m/z=466.1874 for C27H24N5O3.

Workup

  1. customThe reaction mixture was purified directly by HPLC
  2. washeluting with a gradient of H2O
  3. additionThe pure, product-containing fractions
  4. concentrationconcentrated in vacuo
  5. additionThe residue was added to saturated aqueous NaHCO3 (10 mL)
  6. extractionextracted with EtOAc (3×20 mL)
  7. extractionThe combined organic extract
  8. dry with materialwas dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-0cea9cddd35d45a78d31f07c7114cba6
Source dataset
uspto-grants-2010_04
Patent number
US07696192B2

Reaction notes

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