Triethylamine → 4-[1-(2-aminopyrimidin-4-yl)-2-(2-hydroxyethoxy)-1H-1,3-benzodiazol-6-yl]-2-(5-chloropyridin-2-yl)but-3-yn-2-ol

HRID 1398684ノート

反応式

HRID 1398684 の反応式
[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[C:12]3[CH:13]=[C:14](Br)[CH:15]=[CH:16][C:11]=3[N:10]=[C:9]2[O:18][CH2:19][CH2:20][OH:21])[CH:5]=[CH:4][N:3]=1.[Cl:22][C:23]1[CH:24]=[CH:25][C:26]([C:29]([OH:33])([C:31]#[CH:32])[CH3:30])=[N:27][CH:28]=1.C(N(CC)CC)C>CS(C)=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[C:12]3[CH:13]=[C:14]([C:32]#[C:31][C:29]([C:26]4[CH:25]=[CH:24][C:23]([Cl:22])=[CH:28][N:27]=4)([OH:33])[CH3:30])[CH:15]=[CH:16][C:11]=3[N:10]=[C:9]2[O:18][CH2:19][CH2:20][OH:21])[CH:5]=[CH:4][N:3]=1

参加物

6

反応物 3

HCID 8471TriethylamineHCID 681816032-[[1-(2-aminopyrimidin-4-yl)-6-bromo-1H-1,3-benzodiazol-2-yl]oxy]ethan-1-olHCID 866696112-(5-Chloropyridin-2-yl)but-3-yn-2-ol

生成物 1

HCID 681816504-[1-(2-aminopyrimidin-4-yl)-2-(2-hydroxyethoxy)-1H-1,3-benzodiazol-6-yl]-2-(5-chloropyridin-2-yl)but-3-yn-2-ol収率 1%

試薬・触媒・溶媒 2

HCID 178418476HCID 178418476、化合物触媒HCID 679Dimethyl Sulfoxide溶媒

実験手順

A solution of 2-[[1-(2-aminopyrimidin-4-yl)-6-bromo-1H-1,3-benzodiazol-2-yl]oxy]ethan-1-ol (200 mg, 0.57 mmol), 2-(5-chloropyridin-2-yl)but-3-yn-2-ol (518 mg, 2.85 mmol), bis(triphenylphosphine)palladium(II) dichloride (400 mg, 0.57 mmol) and triethylamine (0.5 mL) in DMSO (0.5 mL) was irradiated under nitrogen in a 10-mL sealed tube with microwave radiation for 2 h at 100° C. The reaction mixture was cooled to room temperature and the solid material was removed by filtration. The filtrate was concentrated under vacuum and the crude product (50 mg) was purified by preparative HPLC to give 2 mg (1%) of 4-[1-(2-aminopyrimidin-4-yl)-2-(2-hydroxyethoxy)-1H-1,3-benzodiazol-6-yl]-2-(5-chloropyridin-2-yl)but-3-yn-2-ol as a light yellow solid: 1H NMR (400 MHz, DMSO) delta 8.61 (s, 1H), 8.38 (d, J=5.6 Hz, 1H), 8.16 (s, 1H), 7.98-7.82 (m, 1H), 7.81 (d, J=8.4 Hz, 1H), 7.43 (d, J=8.4 Hz, 1H), 7.26-7.24 (m, 1H), 7.06 (d, J=5.2 Hz, 3H), 6.44 (s, 1H), 5.06 (t, J=5.6 Hz, 1H), 4.61 (t, J=4.8 Hz, 2H), 3.83-3.80 (m, 2H), 1.82 (s, 3H); LC-MS: m/z=+451 (M+H)+.

後処理

  1. customsealed tube with microwave radiation for 2 h at 100° C
  2. customthe solid material was removed by filtration
  3. concentrationThe filtrate was concentrated under vacuum
  4. customthe crude product (50 mg) was purified by preparative HPLC

出典と根拠

ORDレコード
ord-2bb69e7dbb0a4bb491621af3cec98bba
出典データセット
uspto-grants-2014_12
特許番号
US08901313B2

反応ノート

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