Hydrochloric Acid → 5-(benzyloxy)-1-(chloromethyl)-3-[(5-methoxy-1H-indol-2-yl)carbonyl]-2,3-dihydro-1H-pyrrolo[3,2-f]quinoline

HRID 1829606Notes

Reaction equation

HRID 1829606 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[N:21]([C:22](OC(C)(C)C)=[O:23])[CH2:20][CH:19]([CH2:29][Cl:30])[C:12]2=[C:13]2[C:18]=1[N:17]=[CH:16][CH:15]=[CH:14]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[CH3:32][O:33][C:34]1[CH:35]=[C:36]2[C:40](=[CH:41][CH:42]=1)[NH:39][C:38](C(O)=O)=[CH:37]2.CCN=C=NCCCN(C)C>O1CCOCC1.CC(N(C)C)=O>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[N:21]([C:22]([C:38]3[NH:39][C:40]4[C:36]([CH:37]=3)=[CH:35][C:34]([O:33][CH3:32])=[CH:42][CH:41]=4)=[O:23])[CH2:20][CH:19]([CH2:29][Cl:30])[C:12]2=[C:13]2[C:18]=1[N:17]=[CH:16][CH:15]=[CH:14]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 204015-Methoxyindole-2-carboxylic acidHCID 220534015-Benzyloxy-3-(tert-butyloxycarbonyl)-1-(chloromethyl)-2,3-dihydro-1H-pyrrolo[3,2-f]quinoline

Product 1

HCID 220533795-(benzyloxy)-1-(chloromethyl)-3-[(5-methoxy-1H-indol-2-yl)carbonyl]-2,3-dihydro-1H-pyrrolo[3,2-f]quinolineYield 98%

Reagents, catalysts & solvents 2

HCID 312751,4-DioxaneSolventHCID 31374DimethylacetamideSolvent

Procedure

A suspension of 14 (0.10 g, 0.24 mmol) in dioxane (15 mL) was saturated with HCl, stirred at r.t. for 5 h and evaporated. 5-Methoxy-1-H-indole-2-carboxylic acid (0.054 g, 0.28 mmol), EDCI (0.23 g, 1.17 mmol) and DMA (5 mL) were added to the remaining yellow solid, and the red mixture was stirred at r.t. for 52 h. The mixture was partitioned between CH2Cl2 and cold 5% KHCO3 solution. The aqueous layer was extracted with CH2Cl2 (×3). The CH2Cl2 extracts were dried (brine, Na2SO4). Flash chromatography (EtOAc/petroleum ether, 7:3) gave 5-(benzyloxy)-1-(chloromethyl)-3-[(5-methoxy-1H-indol-2-yl)carbonyl]-2,3-dihydro-1H-pyrrolo[3,2-f]quinoline (17d) (0.11 g, 98%) as a yellow solid: mp 186–189° C.; 1H NMR (CDCl3) δ 9.55 (s, 1 H), 8.88 (dd, J=4.2, 1.7, 1 H), 8.37 (s, 1 H), 7.99 (dd, J=8.3, 1.6, 1 H), 7.56 (d, J=7.3, 2 H), 7.42 (dd, J=8.3, 4.1, 1 H), 7.33 (m, 4 H), 7.10 (d, J=2.3, 1 H), 6.99 (m, 2 H), 5.48 (d, J=12.5, 1 H), 5.42 (d, J=12.6, 1 H), 4.74 (dd, J=10.9, 2.0, 1 H), 4.61 (dd, J=10.6, 8.7, 1 H), 4.05 (m, 1 H), 3.85 (s, 3 H), 3.84 (dd, J=11.2, 4.1, 1 H), 3.45 (dd, J=11.0, 10.5, 1 H); 13C NMR (CDCl3) δ 160.7, 155.4, 154.7, 147.9, 142.4, 138.4, 136.4, 131.4, 130.5, 130.2, 128.6, 128.2, 128.0, 127.7, 125.2, 122.4, 117.0, 115.4, 112.7, 106.2, 102.5, 102.4, 70.9, 55.7, 55.2, 45.9, 42.6.

Workup

  1. customevaporated
  2. stirringthe red mixture was stirred at r.t. for 52 h
  3. customThe mixture was partitioned between CH2Cl2 and cold 5% KHCO3 solution
  4. extractionThe aqueous layer was extracted with CH2Cl2 (×3)
  5. dry with materialThe CH2Cl2 extracts were dried (brine, Na2SO4)

Sources & evidence

ORD record
ord-daccda6e3b2d41a39bc95d03cb7395ad
Source dataset
uspto-grants-2006_06
Patent number
US07064117B2

Reaction notes

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