Tetrahydrofuran → 1-(Chloromethyl)-3-[(5-methoxyindol-2-yl)carbonyl]-5-hydroxy-2,3-dihydro-1H-pyrrolo[3,2-f]quinoline

HRID 1829607Notes

Reaction equation

HRID 1829607 reaction equation
C1COCC1.C([O:13][C:14]1[CH:15]=[C:16]2[N:26]([C:27]([C:29]3[NH:30][C:31]4[C:36]([CH:37]=3)=[CH:35][C:34]([O:38][CH3:39])=[CH:33][CH:32]=4)=[O:28])[CH2:25][CH:24]([CH2:40][Cl:41])[C:17]2=[C:18]2[C:23]=1[N:22]=[CH:21][CH:20]=[CH:19]2)C1C=CC=CC=1>O.[Pd]>[Cl:41][CH2:40][CH:24]1[C:17]2=[C:18]3[C:23](=[C:14]([OH:13])[CH:15]=[C:16]2[N:26]([C:27]([C:29]2[NH:30][C:31]4[C:36]([CH:37]=2)=[CH:35][C:34]([O:38][CH3:39])=[CH:33][CH:32]=4)=[O:28])[CH2:25]1)[N:22]=[CH:21][CH:20]=[CH:19]3

Participants

5

Reactant 2

HCID 8028TetrahydrofuranHCID 220533795-(benzyloxy)-1-(chloromethyl)-3-[(5-methoxy-1H-indol-2-yl)carbonyl]-2,3-dihydro-1H-pyrrolo[3,2-f]quinoline

Product 1

HCID 102948471-(Chloromethyl)-3-[(5-methoxyindol-2-yl)carbonyl]-5-hydroxy-2,3-dihydro-1H-pyrrolo[3,2-f]quinolineYield 89%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

THF (6 mL) then HCO2NH4 (0.14 g, 2.21 mmol) in H2O (0.7 mL) were added to cooled (0° C.) mixture of 17d (0.11 g, 0.22 mmol) and 10% Pd/C (0.05 g) under N2. The mixture was stirred at 0° C. for 5 h, and was then filtered through Celite. The Celite was washed with CH2Cl2/H2O. The aqueous layer was extracted with CH2Cl2 (×3). The CH2Cl2 extracts were dried (brine, Na2SO4) and CH2Cl2 evaporated. Precipitation from CH2Cl2/MeOH gave 18d (0.077 g, 89%) as a grey solid: mp 224–227° C.; 1H NMR [(CD3)2SO]δ 11.66 (s, 1 H), 10.02 (bs, 1 H), 8.77 (dd, J=4.1, 1.3, 1 H), 8.41 (dd, J=8.4, 1.4, 1 H), 8.07 (s, 1 H), 7.57 (dd, J=8.4, 4.1, 1 H), 7.40 (d, J=9.0, 1 H), 7.16 (d, J=2.4, 1 H), 7.12 (d, J=1.6, 1 H), 6.92 (dd, J=8.9, 2.3, 1 H), 4.82 (dd, J=10.8, 9.4, 1 H), 4.57 (dd, J=11.0, 2.3, 1 H), 4.30 (m, 1 H), 4.04 (dd, J=11.1, 3.3, 1 H), 3.91 (dd; J=11.1, 7.2, 1 H), 3.78 (s, 3 H).

Workup

  1. temperatureto cooled
  2. filtrationwas then filtered through Celite
  3. washThe Celite was washed with CH2Cl2/H2O
  4. extractionThe aqueous layer was extracted with CH2Cl2 (×3)
  5. dry with materialThe CH2Cl2 extracts were dried (brine, Na2SO4) and CH2Cl2
  6. customevaporated
  7. customPrecipitation from CH2Cl2/MeOH

Sources & evidence

ORD record
ord-073ae9d867cc41a483202df21710b033
Source dataset
uspto-grants-2006_06
Patent number
US07064117B2

Reaction notes

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