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Dichloromethane → 8-fluoro-9-(3-hydroxy-3-methylbut-1-yn-1-yl)-3-((1-methyl-1H-pyrazol-5-yl)methyl)-3,4,5,6-tetrahydro-4,6-methanobenzo[3,4]cyclohepta[1,2-d]imidazole-2-carboxamide

HRID 575440
ノート
印刷プレビュー

反応式

HRID 575440 の反応式
[F:1][C:2]1[C:26](I)=[CH:25][C:5]2[C:6]3[N:10]=[C:9]([C:11]([NH2:13])=[O:12])[N:8]([CH2:14][C:15]4[N:19]([CH3:20])[N:18]=[CH:17][CH:16]=4)[C:7]=3[CH:21]3[CH2:24][CH:23]([C:4]=2[CH:3]=1)[CH2:22]3.[CH3:28][C:29]([OH:33])([C:31]#[CH:32])[CH3:30].ClCCl>N1CCCCC1.CO.[Cu]I.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>[NH3:8].[F:1][C:2]1[C:26]([C:32]#[C:31][C:29]([OH:33])([CH3:30])[CH3:28])=[CH:25][C:5]2[C:6]3[N:10]=[C:9]([C:11]([NH2:13])=[O:12])[N:8]([CH2:14][C:15]4[N:19]([CH3:20])[N:18]=[CH:17][CH:16]=4)[C:7]=3[CH:21]3[CH2:24][CH:23]([C:4]=2[CH:3]=1)[CH2:22]3
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

9

反応物 3

HCID 6344DichloromethaneHCID 82582-Methyl-3-butyn-2-olHCID 866934978-fluoro-9-iodo-3((1-methyl-1H-pyrazol-5-yl)methyl)-3,4,5,6-tetrahydro-4,6-methanobenzo[3,4]cyclohepta[1,2-d]imidazole-2-carboxamide

生成物 2

HCID 222AmmoniaHCID 866934988-fluoro-9-(3-hydroxy-3-methylbut-1-yn-1-yl)-3-((1-methyl-1H-pyrazol-5-yl)methyl)-3,4,5,6-tetrahydro-4,6-methanobenzo[3,4]cyclohepta[1,2-d]imidazole-2-carboxamide
収率 157.1%

試薬・触媒・溶媒 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 178418397HCID 178418397、化合物触媒HCID 887Methanol溶媒HCID 8082Piperidine溶媒

反応条件

温度
50 °C

実験手順

To a solution of 8-fluoro-9-iodo-3-((1-methyl-1H-pyrazol-5-yl)methyl)-3,4,5,6-tetrahydro-4,6-methanobenzo[3,4]cyclohepta[1,2-d]imidazole-2-carboxamide (67 mg, 0.14 mmol) in piperidine (2 mL) was introduced 2-methyl-3-butyn-2-ol (68 mg, 0.81 mmol) and copper(I) iodide (2 mg, 0.01 mmol). The solution was de-oxygenated by nitrogen bubbling for five minutes, then tetrakis(triphenylphosphine)palladium(0) (9 mg, 0.01 mmol) added and bubbling continued for a further two minutes. The pressure tube was closed under an atmosphere of nitrogen and the reaction mixture warmed to 50° C. for 4 hr. After evaporation of the reaction mixture in vacuo, the residue was suspended in ethyl acetate (30 mL) and washed with saturated aqueous sodium bicarbonate (2×10 mL), water (2×10 mL) and brine (10 mL). The organic extract was dried over sodium sulfate, filtered and the filtrate adsorbed onto silica gel in vacuo. Purification of the dry-loaded material by silica gel flash column chromatography (eluent: dichloromethane containing a 0-4% gradient of 7M ammonia in methanol) furnished the title compound (47 mg, 0.11 mmol, 78%) as off-white fine crystals: 1H NMR (500 MHz, CDCl3) δ 1.64-1.72 (m, 8H), 2.43 (br. s., 1H), 2.90 (qd, J=7.93, 3.00 Hz, 2H), 3.31-3.40 (m, 1H), 3.54-3.61 (m, 1H), 3.92 (br. s., 3H), 5.49 (br. s., 1H), 5.87 (s, 2H), 6.83 (d, J=10.09 Hz, 1H), 7.42 (br. s., 1H), 8.42 (d, J=7.57 Hz, 1H); M+1=434.

後処理

  1. custombubbling
  2. waitcontinued for a further two minutes
  3. customThe pressure tube was closed under an atmosphere of nitrogen
  4. customAfter evaporation of the reaction mixture in vacuo
  5. washwashed with saturated aqueous sodium bicarbonate (2×10 mL), water (2×10 mL) and brine (10 mL)
  6. extractionThe organic extract
  7. dry with materialwas dried over sodium sulfate
  8. filtrationfiltered
  9. customPurification of the dry-loaded material by silica gel flash column chromatography (eluent

出典と根拠

ORDレコード
ord-eb6943eac78f40e5a0e57a5a74f265dd
出典データセット
uspto-grants-2015_05
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09034866B2

反応ノート

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