Hydrochloric Acid → 2-(4-{(1E)-3-[5-(benzyloxy)-1-(chloromethyl)-1,2-dihydro-3H-pyrrolo[3,2-f]quinolin-3-yl]-3-oxo-1-propenyl}phenoxy)-N,N-dimethylethanamine

HRID 1829605Notes

Reaction equation

HRID 1829605 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.Cl.[CH3:33][N:34]([CH3:49])[CH2:35][CH2:36][O:37][C:38]1[CH:48]=[CH:47][C:41](/[CH:42]=[CH:43]/C(O)=O)=[CH:40][CH:39]=1.CCN=C=NCCCN(C)C>CC(N(C)C)=O.O1CCOCC1>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[N:21]([C:22](=[O:23])/[CH:43]=[CH:42]/[C:41]3[CH:47]=[CH:48][C:38]([O:37][CH2:36][CH2:35][N:34]([CH3:49])[CH3:33])=[CH:39][CH:40]=3)[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:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 220534015-Benzyloxy-3-(tert-butyloxycarbonyl)-1-(chloromethyl)-2,3-dihydro-1H-pyrrolo[3,2-f]quinolineHCID 692996553-{4-[2-(Dimethylamino)ethoxy]phenyl}prop-2-enoic acid hydrochloride

Product 1

HCID 220533722-(4-{(1E)-3-[5-(benzyloxy)-1-(chloromethyl)-1,2-dihydro-3H-pyrrolo[3,2-f]quinolin-3-yl]-3-oxo-1-propenyl}phenoxy)-N,N-dimethylethanamineYield 70.7%

Reagents, catalysts & solvents 2

HCID 312751,4-DioxaneSolventHCID 31374DimethylacetamideSolvent

Procedure

A suspension of 14 (0.20 g, 0.47 mmol) in cooled (0° C.) dioxane (5 mL) was saturated with HCl, allowed to warm to r.t. over 1 h and evaporated. (E)-4-[2-(Dimethylamino)ethoxy]cinnamic acid hydrochloride (0.13 g, 0.47 mmol) [Atwell et al., J. Med. Chem., 1999, 42, 3400], EDCI (0.27 g, 1.42 mmol) and DMA (3 mL) were added to the remaining yellow solid, and the red mixture was stirred at r.t. for 30 h. The mixture was partitioned between CH2Cl2 and 5% NaHCO3 solution. The aqueous layer was extracted with CH2Cl2 (×3). The CH2Cl2 extracts were dried (brine, Na2SO4). Flash chromatography (Alumina, EtOAc/MeOH; 49:1, then 24:1) gave 2-(4-{(1E)-3-[5-(benzyloxy)-1-(chloromethyl)-1,2-dihydro-3H-pyrrolo[3,2-f]quinolin-3-yl]-3-oxo-1-propenyl}phenoxy)-N,N-dimethylethanamine (17c) (0.18 g, 70%) as a yellow solid: mp 172–175° C.; 1H NMR [(CD3)2SO]δ 8.76 (dd, J=4.1, 1.4, 1 H), 8.47 (bs, 1 H), 8.35 (dd, J=8.5, 1.4, 1 H), 7.76 (d, J=8.7, 2 H), 7.67 (d, J=15.3, 1 H), 7.58 (d, J=7.3, 2 H), 7.54 (dd, J=8.5, 4.1, 1 H), 7.44 (t, J=7.2, 2 H), 7.37 (t, J=7.2, 1 H), 7.08 (d, J=15.3, 1 H), 7.02 (d, J=8.7, 2 H), 5.31 (s, 2 H), 4.55 (dd, J=10.7, 9.5, 1 H), 4.44 (dd, J=10.9, 2.5, 1 H), 4.30 (m, 1 H), 4.11 (t, J=5.8, 2 H), 3.99 (dd, J=11.0, 3.0, 1 H), 3.91 (dd, J=11.2, 7.2, 1 H), 2.64 (t, J=5.7, 2 H), 2.23 (s, 6 H); 13C NMR [(CD3)2SO]δ 164.1, 160.1, 154.6, 147.1, 142.6, 142.2, 137.2, 136.7, 131.1, 130.1, 128.3, 127.83, 127 78, 127.3, 125.1, 122.3, 116.9, 115.7, 114.7, 101.6, 70.0, 65.9, 57.5, 52.9, 47.8, 45.4, 40.1.

Workup

  1. customevaporated
  2. customThe mixture was partitioned between CH2Cl2 and 5% NaHCO3 solution
  3. extractionThe aqueous layer was extracted with CH2Cl2 (×3)
  4. dry with materialThe CH2Cl2 extracts were dried (brine, Na2SO4)

Sources & evidence

ORD record
ord-618acf5f98a7488aae50b6cbf301044e
Source dataset
uspto-grants-2006_06
Patent number
US07064117B2

Reaction notes

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