Acetic Acid → Ethyl [4-oxo-1-{[(7S)-2'-oxo-1',2',6,8-tetrahydrospiro[cyclopenta[g]quinoline-7,3'-pyrrolo[2,3-b]pyridin]-2-yl]methyl}-1,2,4,5-tetrahydropyrrolo[4,3,2-de]quinolin-2a(3H)-yl]acetate

HRID 551097Notes

Reaction equation

HRID 551097 reaction equation
[O:1]=[C:2]1[NH:10][C:5]2=[N:6][CH:7]=[CH:8][CH:9]=[C:4]2[C@:3]21[CH2:24][C:13]1[CH:14]=[C:15]3[C:20](=[CH:21][C:12]=1[CH2:11]2)[N:19]=[C:18]([CH:22]=O)[CH:17]=[CH:16]3.[O:25]=[C:26]1[CH2:35][C:34]2([CH2:38][C:39]([O:41][CH2:42][CH3:43])=[O:40])[CH2:36][NH:37][C:32]3[C:33]2=[C:28]([CH:29]=[CH:30][CH:31]=3)[NH:27]1.CC(O)=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[O:25]=[C:26]1[CH2:35][C:34]2([CH2:38][C:39]([O:41][CH2:42][CH3:43])=[O:40])[CH2:36][N:37]([CH2:22][C:18]3[CH:17]=[CH:16][C:15]4[C:20](=[CH:21][C:12]5[CH2:11][C@:3]6([C:4]7[C:5](=[N:6][CH:7]=[CH:8][CH:9]=7)[NH:10][C:2]6=[O:1])[CH2:24][C:13]=5[CH:14]=4)[N:19]=3)[C:32]3[C:33]2=[C:28]([CH:29]=[CH:30][CH:31]=3)[NH:27]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 57663768ethyl (4-oxo-1,2,4,5-tetrahydropyrrolo[4,3,2-de]quinolin-2a(3H)-yl)acetateHCID 59594285(S)-2'-Oxo-1',2',6,8-tetrahydrospiro[cyclopenta[g]quinoline-7,3'-pyrrolo[2,3-b]pyridine]-2-carbaldehyde2×

Product 1

HCID 57663754Ethyl [4-oxo-1-{[(7S)-2'-oxo-1',2',6,8-tetrahydrospiro[cyclopenta[g]quinoline-7,3'-pyrrolo[2,3-b]pyridin]-2-yl]methyl}-1,2,4,5-tetrahydropyrrolo[4,3,2-de]quinolin-2a(3H)-yl]acetate

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a stirred solution of (S)-2′-oxo-1′,2′,6,8-tetrahydrospiro[cyclopenta[g]quinoline-7,3′-pyrrolo[2,3-b]pyridine]-2-carbaldehyde (339 mg, 1.08 mmol, described in Intermediate 10), ethyl (4-oxo-1,2,4,5-tetrahydropyrrolo[4,3,2-de]quinolin-2a(3H)-yl)acetate, enantiomer A (200 mg, 0.768 mmol, described in Intermediate 22), and AcOH (0.44 mL, 7.68 mmol) in DCE (5 mL) was added sodium triacetoxyborohydride (228 mg, 1.08 mmol) and the mixture was stirred for 90 min at ambient temperature. The reaction mixture was partitioned between saturated aqueous NaHCO3 (20 mL) and CH2Cl2 (20 mL). The organic layer was removed and the aqueous layer was extracted further with CH2Cl2 (3×20 mL). The combined organic extracts were washed with brine (10 mL), dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by silica gel chromatography, eluting with a gradient of CH2Cl2:MeOH—100:0 to 95:5, to give the title compound. MS: m/z=560 (M+1). HRMS: m/z=560.2303; calculated m/z=560.2293 for C33H30N5O4.

Workup

  1. customThe reaction mixture was partitioned between saturated aqueous NaHCO3 (20 mL) and CH2Cl2 (20 mL)
  2. customThe organic layer was removed
  3. extractionthe aqueous layer was extracted further with CH2Cl2 (3×20 mL)
  4. washThe combined organic extracts were washed with brine (10 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by silica gel chromatography
  9. washeluting with a gradient of CH2Cl2

Sources & evidence

ORD record
ord-19594fdcb58e4af9a9f429ea3b7f47bb
Source dataset
uspto-grants-2011_05
Patent number
US07947677B2

Reaction notes

Loading…