Triethylamine → 3,3-dimethyl-N-(3-{[4-(trifluoromethoxy)phenyl]ethynyl}pyrazolo[1,5-a]pyrimidin-2-yl)butanamide

HRID 1912960

反応式

HRID 1912960 の反応式
C(N(CC)CC)C.[C:8]([C:10]1[CH:15]=[CH:14][C:13]([O:16][C:17]([F:20])([F:19])[F:18])=[CH:12][CH:11]=1)#[CH:9].[CH3:21][C:22]([CH3:43])([CH3:42])[CH2:23][C:24]([NH:26][C:27]1[C:35](C2C=NC=CC=2)=[C:30]2[N:31]=[CH:32][CH:33]=[CH:34][N:29]2[N:28]=1)=[O:25]>O1CCCC1.C(P([Pd]P(C(C)(C)C)(C(C)(C)C)C(C)(C)C)(C(C)(C)C)C(C)(C)C)(C)(C)C.[Cu]I>[CH3:21][C:22]([CH3:43])([CH3:42])[CH2:23][C:24]([NH:26][C:27]1[C:35]([C:9]#[C:8][C:10]2[CH:11]=[CH:12][C:13]([O:16][C:17]([F:18])([F:19])[F:20])=[CH:14][CH:15]=2)=[C:30]2[N:31]=[CH:32][CH:33]=[CH:34][N:29]2[N:28]=1)=[O:25]

参加物

7

反応物 3

HCID 8471TriethylamineHCID 27784941-Ethynyl-4-(trifluoromethoxy)benzeneHCID 68751160HCID 68751160、化合物

生成物 1

HCID 687489723,3-dimethyl-N-(3-{[4-(trifluoromethoxy)phenyl]ethynyl}pyrazolo[1,5-a]pyrimidin-2-yl)butanamide

試薬・触媒・溶媒 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 178454917HCID 178454917、化合物触媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
85 °C

実験手順

Triethylamine (3 mL) was added to a mixture of bis(tri-t-butylphosphino)palladium (9.6 mg, 0.019 mmol; Strem), 1-ethynyl-4-trifluoromethoxybenzene (0.12 mL, 0.75 mmol), CuI (3.6 mg, 0.019 mmol) and the product from Example 110B (117 mg, 0.38 mmol) in anhydrous tetrahydrofuran (3 mL). The mixture was purged with a nitrogen stream for 2 minutes, and then stirred at 85° C. for 18 hours in a sealed tube. The reaction mixture was cooled and partitioned between dichloromethane (2×50 mL) and 1.0 M sodium carbonate (100 mL). The combined organic extracts were dried (sodium sulfate), filtered, and concentrated under vacuum. The resulting residue was purified by reverse-phase HPLC [Waters XBridge™ RP18 column, 5 μm, 30×100 mm, flow rate 40 mL/minute, 20-100% gradient of acetonitrile in buffer (0.1 M aqueous ammonium bicarbonate, adjusted to pH 10 with ammonium hydroxide)] to afford the title compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.34 (s, 1H), 9.12 (dd, J=6.9, 1.7 Hz, 1H), 8.65 (dd, J=4.1, 1.7 Hz, 1H), 7.58-7.60 (m, 2H), 7.41-7.44 (m, 2H), 7.17 (dd, J=6.9, 4.1 Hz, 1H), 2.29 (s, 2H), 1.07 (s, 9H); MS (APCI) m/z 417 (M+H)+.

後処理

  1. customThe mixture was purged with a nitrogen stream for 2 minutes
  2. temperatureThe reaction mixture was cooled
  3. custompartitioned between dichloromethane (2×50 mL) and 1.0 M sodium carbonate (100 mL)
  4. dry with materialThe combined organic extracts were dried (sodium sulfate)
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customThe resulting residue was purified by reverse-phase HPLC [Waters XBridge™ RP18 column, 5 μm, 30×100 mm, flow rate 40 mL/minute, 20-100% gradient of acetonitrile in buffer (0.1 M aqueous ammonium bicarbonate, adjusted to pH 10 with ammonium hydroxide)]

出典と根拠

ORDレコード
ord-d5856cb40729443abb1cbb88c326cd2f
出典データセット
uspto-grants-2013_12
特許番号
US08609669B2

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