Hydrochloric Acid → 2-[(2-{[5-(benzyloxy)-1-(chloromethyl)-1,2-dihydro-3H-pyrrolo[3,2-f]quinolin-3-yl]carbonyl}-1H-indol-5-yl)oxy]-N,N-dimethylethanamine

HRID 1829603ノート

反応式

HRID 1829603 の反応式
[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]([CH3:50])[CH2:35][CH2:36][O:37][C:38]1[CH:39]=[C:40]2[C:44](=[CH:45][CH:46]=1)[NH:43][C:42](C(O)=O)=[CH:41]2.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]([C:42]3[NH:43][C:44]4[C:40]([CH:41]=3)=[CH:39][C:38]([O:37][CH2:36][CH2:35][N:34]([CH3:50])[CH3:33])=[CH:46][CH:45]=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:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

参加物

7

反応物 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 686908585-[2-(Dimethylamino)ethoxy]indole-2-carboxylic acid hydrochloride

生成物 1

HCID 220534002-[(2-{[5-(benzyloxy)-1-(chloromethyl)-1,2-dihydro-3H-pyrrolo[3,2-f]quinolin-3-yl]carbonyl}-1H-indol-5-yl)oxy]-N,N-dimethylethanamine収率 84.3%

試薬・触媒・溶媒 2

HCID 312751,4-Dioxane溶媒HCID 31374Dimethylacetamide溶媒

実験手順

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 2 h and evaporated. 5-[2-(Dimethylamino)ethoxy]-1-H-indole-2-carboxylic acid hydrochloride (0.13 g, 0.47 mmol) [Milbank et al., J. Med. Chem., 1999, 42, 649], 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 20 h. The mixture was partitioned between EtOAc and 5% NaHCO3 solution. The aqueous layer was extracted with EtOAc (×3). The EtOAc extracts were dried (brine, Na2SO4). Flash chromatography (Alumina, EtOAc/MeOH; 49:1, then 9:1) gave 2-[(2-{[5-(benzyloxy)-1-(chloromethyl)-1,2-dihydro-3H-pyrrolo[3,2-f]quinolin-3-yl]carbonyl}-1H-indol-5-yl)oxy]-N,N-dimethylethanamine (17b) (0.22 g, 84%) as a yellow solid: mp 176–179° C.; 1H NMR [(CD3)2SO]δ 11.68 (s, 1 H), 8.79 (dd, J=4.1, 1.5 Hz, 1 H), 8.41 (dd, J=8.6, 1.5 Hz, 1 H), 8.29 (s, 1 H ), 7.56 (m, 3 H), 7.40 (m, 4 H), 7.17 (d, J=2.3 Hz, 1 H ), 7.11 (d, J=1.5 Hz, 1 H), 6.92 (dd, J=9.0, 2.4 Hz, 1 H), 5.32 (s, 2 H), 4.82 (dd, J=10.7, 9.6 Hz, 1 H), 4.58 (dd, J=10.9, 2.1 Hz, 1 H), 4.32 (m, 1 H), 4.05 (t, J=5.7 Hz, 2 H), 4.04 (m, 1 H), 3.93 (dd, J=11.2, 6.9 Hz, 1 H), 2.65 (t, J=5.8 Hz, 2 H), 2.23 (s, 6H); 13C NMR [(CD3)2SO]δ 160.3, 154.5, 153.0, 147.3, 142.3, 137.4, 136.7, 131.6, 131.3, 130.6,128.4, 127.9, 127.7, 127.4, 125.1, 122.4, 116.2, 116.0, 113.1, 105.5, 103.1, 102.0, 70.0, 66.9, 66.2, 57.8, 54.9, 47.7, 45.5, 40.7.

後処理

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

出典と根拠

ORDレコード
ord-7e41c59e82f14ae08568aafeaf70e0f6
出典データセット
uspto-grants-2006_06
特許番号
US07064117B2

反応ノート

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