Ammonium Chloride → 8-{[(2-chloropyridin-3-yl)carbonyl]amino}-1-(4-ethynylphenyl)-4,5-dihydro-1H-benzo[g]indazole-3-carboxamide

HRID 457334ノート

反応式

HRID 457334 の反応式
[NH2:1][C:2]1[CH:24]=[CH:23][C:5]2[CH2:6][CH2:7][C:8]3[C:9]([C:20]([NH2:22])=[O:21])=[N:10][N:11]([C:13]4[CH:18]=[CH:17][C:16](Br)=[CH:15][CH:14]=4)[C:12]=3[C:4]=2[CH:3]=1.[Si]([C:32]#[CH:33])(C(C)(C)C)(C)C.[Cl:34][C:35]1[N:42]=[CH:41][CH:40]=[CH:39][C:36]=1[CH2:37]Cl.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[Cl-].[NH4+].CN(C=[O:67])C.C(N(CC)CC)C>[Cu]I.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[Cl:34][C:35]1[C:36]([C:37]([NH:1][C:2]2[CH:24]=[CH:23][C:5]3[CH2:6][CH2:7][C:8]4[C:9]([C:20]([NH2:22])=[O:21])=[N:10][N:11]([C:13]5[CH:18]=[CH:17][C:16]([C:32]#[CH:33])=[CH:15][CH:14]=5)[C:12]=4[C:4]=3[CH:3]=2)=[O:67])=[CH:39][CH:40]=[CH:41][N:42]=1

参加物

9

反応物 6

HCID 25517Ammonium ChlorideHCID 2724141Tetrabutylammonium FluorideHCID 2757281(tert-Butyldimethylsilyl)acetyleneHCID 115283992-Chloro-3-chloromethyl-pyridineHCID 22056947triethylamine N,N-dimethylformamideHCID 222915188-amino-1-(4-bromophenyl)-4,5-dihydro-1H-benzo[g]indazole-3-carboxamide

生成物 1

HCID 222915468-{[(2-chloropyridin-3-yl)carbonyl]amino}-1-(4-ethynylphenyl)-4,5-dihydro-1H-benzo[g]indazole-3-carboxamide

試薬・触媒・溶媒 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 11979704Tetrakis(triphenylphosphine)palladium触媒

反応条件

温度
100 °C

実験手順

A stirred solution of 8-amino-1-(4-bromophenyl)-4,5-dihydro-1H-benzo[g]indazole-3-carboxamide (5.74 g, 15 mmol) and tert-butyldimethylsilylacetylene (2.31 g, 16.5 mmol) in DMF-triethylamine (20 mL-10 mL) was added CuI (285 mg, 1.5 mmol) and tetrakis(triphenylphosphine) palladium (870 mg, 0.75 mmol) and the resulted mixture was heated at 100° C. for 14 h before cooled to rt. The mixture was filtered through silica gel pad, washed with EtOAc, and concentrated. The crude material was taken into pyridine (30 mL), treated with 2-chloronicotinyl chloride (2.90 g, 16.5 mmol) at RT for 14 h. Tetrabutylammonium fluoride (25 mL of 1M THF solution, 25 mmol) was added at RT and stirred overnight. Aqueous ammonium chloride was added, the mixture extracted with EtOAc (5×30 mL). The organic portions were combined, dried over MgSO4, filtered, and separated by silica gel column (EtOAc). This gave product as a pale yellow solid (3.5 g, 49% over 3 steps). 1H NMR was consistent with its structure. CNH calculated for C26H18N5O2Cl(H2O)1.3: C(63.5%), H(4.2%), N(14.3%); found: C(63.6%), H(4.0%), N(14.3%).

後処理

  1. temperaturebefore cooled to rt
  2. filtrationThe mixture was filtered through silica gel pad
  3. washwashed with EtOAc
  4. concentrationconcentrated
  5. extractionthe mixture extracted with EtOAc (5×30 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customseparated by silica gel column (EtOAc)

出典と根拠

ORDレコード
ord-d26e512405054e6fa896bac84b0d91fc
出典データセット
uspto-grants-2007_03
特許番号
US07186743B2

反応ノート

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