1,2-Dichloroethane → (E)-N-(3-methoxy-2-propoxybenzyl)-N-methyl-3-(5-methyl-4-oxo-1,2,3,4,5,6-hexahydropyrido[2,3-b][1,5]diazocin-8-yl)acrylamide

HRID 1880012ノート

反応式

HRID 1880012 の反応式
C(Cl)CCl.Cl.[CH3:6][N:7]1[C:14](=[O:15])[CH2:13][CH2:12][NH:11][C:10]2[N:16]=[CH:17][C:18](/[CH:20]=[CH:21]/[C:22]([OH:24])=O)=[CH:19][C:9]=2[CH2:8]1.C1C=CC2N(O)N=NC=2C=1.[CH3:35][O:36][C:37]1[C:38]([O:46][CH2:47][CH2:48][CH3:49])=[C:39]([CH2:43][NH:44][CH3:45])[CH:40]=[CH:41][CH:42]=1.C(N(C(C)C)C(C)C)C>CN(C=O)C.C(#N)CC.C(OCC)(=O)C>[CH3:35][O:36][C:37]1[C:38]([O:46][CH2:47][CH2:48][CH3:49])=[C:39]([CH:40]=[CH:41][CH:42]=1)[CH2:43][N:44]([CH3:45])[C:22](=[O:24])/[CH:21]=[CH:20]/[C:18]1[CH:17]=[N:16][C:10]2[NH:11][CH2:12][CH2:13][C:14](=[O:15])[N:7]([CH3:6])[CH2:8][C:9]=2[CH:19]=1

参加物

8

反応物 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 28338626(3-Methoxy-2-propoxybenzyl)methylamineHCID 68413470(E)-3-(5-methyl-4-oxo-1,2,3,4,5,6-hexahydropyrido[2,3-b][1,5]diazocin-8-yl)acrylic acid hydrochloride

生成物 1

HCID 24891612(E)-N-(3-methoxy-2-propoxybenzyl)-N-methyl-3-(5-methyl-4-oxo-1,2,3,4,5,6-hexahydropyrido[2,3-b][1,5]diazocin-8-yl)acrylamide

試薬・触媒・溶媒 2

HCID 8857Ethyl Acetate溶媒HCID 86641869DMF propionitrile溶媒

反応条件

温度
40 °C

実験手順

EDC (54 mg, 0.28 mmol) was added to a suspension of (E)-3-(5-methyl-4-oxo-1,2,3,4,5,6-hexahydropyrido[2,3-b][1,5]diazocin-8-yl)acrylic acid hydrochloride (70 mg, 0.23 mmol), HOBt (34 mg, 0.25 mmol), (3-methoxy-2-propoxyphenyl)-N-methylmethanamine (52 mg, 0.25 mmol) and (i-Pr)2EtN (0.20 mL, 1.2 mmol) in 5 mL of DMF:propionitrile (4:1). The mixture was allowed to stir for 17 h at 40° C. The mixture was cooled to room temperature and diluted with ethyl acetate (40 mL) and washed with water (50 mL) and NaHCO3 (50 mL), dried over MgSO4 and dried under high vacuum. The solid was then subjected to purification on Prep HPLC to obtain the product as a fluffy white solid. Yield 64 mg (62%); 1H NMR (400 MHz, CDCl3) δ 7.87 (s, 1H), 7.73 (s, 1H), 7.50 (m, 2H), 7.05 (m, 1H), 6.86 (m, 2H), 6.73 (d, J=7.6 Hz, 1H), 4.72 (s, 3H), 4.00 (m, 2H), 3.89 (s, 5H), 3.14 (m, 5H), 2.83 (s, 3H), 1.82 (q, J=6.8 Hz, 2H), 1.06 (t, J=7.6 Hz, 3H); ESI MS m/z 453 [C25H32N4O4+H]+

後処理

  1. temperatureThe mixture was cooled to room temperature
  2. washwashed with water (50 mL) and NaHCO3 (50 mL)
  3. dry with materialdried over MgSO4
  4. customdried under high vacuum
  5. customThe solid was then subjected to purification on Prep HPLC

出典と根拠

ORDレコード
ord-c775bc2d6d3b4bc4b39f1524aa85b701
出典データセット
uspto-grants-2012_11
特許番号
US08318720B2

反応ノート

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