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4-Fluorophenylboronic acid → 1-[7-(2-Chlorophenyl)-8-(4-fluorophenyl)-2-methylpyrazolo[1,5-a][1,3,5]triazin-4-yl]-4-ethylaminopiperidine-4-carboxylic acid amide

HRID 2054413
ノート
印刷プレビュー

反応式

HRID 2054413 の反応式
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:29](I)=[C:11]2[N:12]=[C:13]([CH3:28])[N:14]=[C:15]([N:16]3[CH2:21][CH2:20][C:19]([NH:25][CH2:26][CH3:27])([C:22]([NH2:24])=[O:23])[CH2:18][CH2:17]3)[N:10]2[N:9]=1.[F:31][C:32]1[CH:37]=[CH:36][C:35](B(O)O)=[CH:34][CH:33]=1>C(O)C.C1(C)C=CC=CC=1.C([O-])([O-])=O.[Na+].[Na+].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:29]([C:35]2[CH:36]=[CH:37][C:32]([F:31])=[CH:33][CH:34]=2)=[C:11]2[N:12]=[C:13]([CH3:28])[N:14]=[C:15]([N:16]3[CH2:21][CH2:20][C:19]([NH:25][CH2:26][CH3:27])([C:22]([NH2:24])=[O:23])[CH2:18][CH2:17]3)[N:10]2[N:9]=1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

7

反応物 2

HCID 2856454-Fluorophenylboronic acidHCID 596557211-[7-(2-Chlorophenyl)-8-iodo-2-methylpyrazolo[1,5-a][1,3,5]triazin-4-yl]-4-ethylaminopiperidine-4-carboxylic Acid Amide

生成物 1

HCID 113756131-[7-(2-Chlorophenyl)-8-(4-fluorophenyl)-2-methylpyrazolo[1,5-a][1,3,5]triazin-4-yl]-4-ethylaminopiperidine-4-carboxylic acid amide収率 266%

試薬・触媒・溶媒 4

HCID 178418397
HCID 178418397、化合物
触媒
HCID 702Ethanol溶媒
HCID 1140Toluene溶媒
HCID 10340Sodium Carbonate溶媒

反応条件

温度
80 °C

実験手順

A mixture of 1-[7-(2-chlorophenyl)-8-iodo-2-methylpyrazolo[1,5-a][1,3,5]triazin-4-yl]4-ethylaminopiperidine-4-carboxylic acid amide (I-1A-1i; 20 mg, 0.037 mmol) and 4-fluorophenylboronic acid (7.8 mg, 0.056 mmol) in ethanol (1.3 ml), toluene (1.3 ml) and 2M aqueous Na2CO3 (0.3 ml) was degassed (3×) by pulling a vacuum followed by refilling with nitrogen gas. Tetrakis(triphenylphosphine)palladium (6 mg, 0.005 mmol) was added and the mixture was heated at 80° C. for 5 hours. After cooling to room temperature, the mixture was extracted from water with ethyl acetate, the combined organic layers were washed with brine, dried (MgSO4), filtered through a 0.45 μm filter disk, and then concentrated, in vacuo, to afford the crude product (50 mg). Purification on a Chromatotron using 0-3% methanol in methylene chloride as eluant afforded a light yellow oil, which was crystallized from diethyl ether, and dried, in vacuo, to afford 1A-1 (11 mg, 58%) as a colorless solid: +ESI MS (M+1) 508.4; 1H NMR (400 MHz, CD3OD) δ 7.46-7.34 (m, 4H), 7.32 (dd, J=8.7, 5.4 Hz, 2H), 6.96 (t, J=8.7 Hz), 4.70-4.58 (br m, 2H), 4.40-4.25 (br m, 2H), 2.51 (q, J=7.1 Hz, 2H), 2.46 (s, 3H), 2.20-2.12 (br m, 2H), 1.83-1.75 (m, 2H), 1.10 (t, J=7.1 Hz, 3H).

後処理

  1. customwas degassed (3×)
  2. temperatureAfter cooling to room temperature
  3. extractionthe mixture was extracted from water with ethyl acetate
  4. washthe combined organic layers were washed with brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered through a 0.45 μm
  7. filtrationfilter disk
  8. concentrationconcentrated, in vacuo

出典と根拠

ORDレコード
ord-b4aa9e49570c4ad6bff8e0e539a91513
出典データセット
uspto-grants-2008_02
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07329658B2

反応ノート

読み込み中…

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