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

HRID 340841ノート

反応式

HRID 340841 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][NH:36][CH2:37][C:38]1[S:42][C:41]2[CH:43]=[CH:44][CH:45]=[CH:46][C:40]=2[C:39]=1[CH3:47].C(N(C(C)C)C(C)C)C>COCCOC.C(#N)CC.C(OCC)(=O)C>[CH3:35][N:36]([CH2:37][C:38]1[S:42][C:41]2[CH:43]=[CH:44][CH:45]=[CH:46][C:40]=2[C:39]=1[CH3:47])[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 22593745N-methyl(3-methylbenzo[b]thiophen-2-yl)methanamineHCID 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 24891613(E)-N-methyl-3-(5-methyl-4-oxo-1,2,3,4,5,6-hexahydropyrido[2,3-b][1,5]diazocin-8-yl)-N-((3-methylbenzo[b]thiophen-2-yl)methyl)acrylamide

試薬・触媒・溶媒 2

HCID 8857Ethyl Acetate溶媒HCID 86695570DME 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), N-methyl(3-methylbenzo[b]thiophen-2-yl)methanamine (48 mg, 0.25 mmol) and (i-Pr)2EtN (0.20 mL, 1.2 mmol) in 5 mL of DME:propionitrile (4:1). The mixture was allowed to stir for 1 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 54 mg (54%); 1H NMR (400 MHz, CDCl3) δ10.41 (bs, 1H), 8.08 (s, 1H), 7.79-7.68 (m, 3H), 7.59 (d, J=15.2 Hz, 1H), 7.40 (m, 2H), 6.95-6.86 (m, 1H), 4.96 (s, 2H), 4.72 (bs, 2H), 3.90 (s, 2H), 3.15 (m, 5H), 2.84 (s, 3H), 2.46 (s, 3H); ESI MS m/z 435 [C24H26N4O2S+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-cc312a132ca540ef9d1010cd791a9b6b
出典データセット
uspto-grants-2014_11
特許番号
US08895545B2

反応ノート

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