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Sodium Carbonate → 4-(7-fluoro-1H-indol-6-yl)-7-(4-methylpiperazine-1-carbonyl)-9H-carbazole-1-carboxamide

HRID 1811085
ノート
印刷プレビュー

反応式

HRID 1811085 の反応式
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]([C:10]2[CH:22]=[C:21]3[C:13]([C:14]4[C:15](B5OC(C)(C)C(C)(C)O5)=[CH:16][CH:17]=[C:18]([C:23]([NH2:25])=[O:24])[C:19]=4[NH:20]3)=[CH:12][CH:11]=2)=[O:9])[CH2:4][CH2:3]1.Br[C:36]1[C:44]([F:45])=[C:43]2[C:39]([CH:40]=[CH:41][NH:42]2)=[CH:38][CH:37]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.C(O)C.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>[F:45][C:44]1[C:36]([C:15]2[C:14]3[C:13]4[C:21](=[CH:22][C:10]([C:8]([N:5]5[CH2:4][CH2:3][N:2]([CH3:1])[CH2:7][CH2:6]5)=[O:9])=[CH:11][CH:12]=4)[NH:20][C:19]=3[C:18]([C:23]([NH2:25])=[O:24])=[CH:17][CH:16]=2)=[CH:37][CH:38]=[C:39]2[C:43]=1[NH:42][CH:41]=[CH:40]2
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 3

HCID 10340Sodium CarbonateHCID 591331976-Bromo-7-fluoro-1H-indoleHCID 666059127-(4-methylpiperazine-1-carbonyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-9H-carbazole-1-carboxamide

生成物 1

HCID 468340984-(7-fluoro-1H-indol-6-yl)-7-(4-methylpiperazine-1-carbonyl)-9H-carbazole-1-carboxamide収率 30%

試薬・触媒・溶媒 3

HCID 178418397
HCID 178418397、化合物
触媒
HCID 702Ethanol溶媒
HCID 1140Toluene溶媒

反応条件

温度
90 °C

実験手順

A mixture of 7-(4-methylpiperazine-1-carbonyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-9H-carbazole-1-carboxamide (prepared according to the procedure of Step 1 of Example 2-1, 75 mg, 0.065 mmol), 6-bromo-7-fluoro-1H-indole (prepared according to U.S. pat. appl. 2007/112005, 18.7 mg, 0.087 mmol), and 2 M aqueous sodium carbonate (0.081 mL, 0.162 mmol) in toluene (0.8 mL) and ethanol (0.2 mL) was purged with argon, treated with tetrakis(triphenylphosphine)palladium (7.5 mg, 0.007 mmol) and heated at 90° C. After 16 h, the mixture was cooled to rt. The residue was purified by preparative HPLC. The resulting TFA salt was partitioned between NaHCO3 (aq) and EtOAc, and the organic extracts were dried and concentrated to provide 4-(7-fluoro-1H-indol-6-yl)-7-(4-methylpiperazine-1-carbonyl)-9H-carbazole-1-carboxamide as an off-white solid (9 mg, 30%). 1H NMR (400 MHz, methanol-d4) δ 7.99 (d, J=7.5 Hz, 1H) 7.68 (d, J=0.9 Hz, 1H) 7.52 (d, J=7.9 Hz, 1H) 7.39 (d, J=3.5 Hz, 1H) 7.25 (dd, J=8.1, 1.1 Hz, 1H) 7.21 (d, J=7.5 Hz, 1H) 7.08 (dd, J=8.1, 6.4 Hz, 1H) 6.92 (dd, J=8.1, 1.5 Hz, 1H) 6.63 (t, J=3.3 Hz, 1H) 3.77 (br. s., 2H) 3.49 (br. s., 2H) 2.51 (br. s., 2H) 2.39 (br. s., 2H) 2.30 (s, 3H). Mass spectrum m/z 470.1 (M+H)+.

後処理

  1. customprepared
  2. customwas purged with argon
  3. temperaturethe mixture was cooled to rt
  4. customThe residue was purified by preparative HPLC
  5. customThe resulting TFA salt was partitioned between NaHCO3 (aq) and EtOAc
  6. customthe organic extracts were dried
  7. concentrationconcentrated

出典と根拠

ORDレコード
ord-02ab85015c164b31bfae6f181ccbab6a
出典データセット
uspto-grants-2013_01
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08362065B2

反応ノート

読み込み中…

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