Hydrochloric Acid → HCID 178463549、化合物

HRID 510916ノート

反応式

HRID 510916 の反応式
[Cl:1][C:2]1[CH:7]=[C:6]([C:8]2[CH:9]=[N:10][N:11](C(OCC)C)[CH:12]=2)[C:5]([C:18]2[CH:23]=[C:22]([F:24])[CH:21]=[C:20]([F:25])[CH:19]=2)=[C:4]([CH:26]([NH2:28])[CH3:27])[CH:3]=1.Br[C:30]1[N:38]=[CH:37][N:36]=[C:35]2[C:31]=1[N:32]=[CH:33][N:34]2C1CCCCO1.C(N(CC)C(C)C)(C)C.Cl.O>C(O)C.CO>[Cl:1][C:2]1[CH:7]=[C:6]([C:8]2[CH:12]=[N:11][NH:10][CH:9]=2)[C:5]([C:18]2[CH:23]=[C:22]([F:24])[CH:21]=[C:20]([F:25])[CH:19]=2)=[C:4]([CH:26]([NH:28][C:30]2[N:38]=[CH:37][N:36]=[C:35]3[C:31]=2[N:32]=[CH:33][NH:34]3)[CH3:27])[CH:3]=1

参加物

8

反応物 5

HCID 313Hydrochloric AcidHCID 962WaterHCID 81531DiisopropylethylamineHCID 583686166-Bromo-9-(tetrahydro-2H-pyran-2-YL)-9H-purineHCID 679691831-{4-Chloro-6-[1-(1-ethoxyethyl)-1H-pyrazol-4-yl]-3',5'-difluorobiphenyl-2-yl}ethanamine

生成物 1

HCID 178463549HCID 178463549、化合物収率 43%

試薬・触媒・溶媒 2

HCID 702Ethanol溶媒HCID 887Methanol溶媒

反応条件

温度
90 °C

実験手順

A solution of 1-{4-chloro-6-[1-(1-ethoxyethyl)-1H-pyrazol-4-yl]-3′,5′-difluorobiphenyl-2-yl}ethanamine (60 mg, 0.15 mmol), 6-bromo-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (63 mg, 0.22 mmol, from Example 108, Step 1), and N,N-diisopropylethylamine (77 μL, 0.44 mmol) in ethanol (2.8 mL) was heated in the microwave at 130° C. for 30 minutes. Alternatively, this reaction can be heated at 90° C. overnight on the benchtop. The reaction mixture was cooled to room temperature, treated with 6 M Hydrogen chloride in water (0.49 mL, 3.0 mmol), and stirred for 30 minutes. The reaction mixture was diluted slightly with methanol, filtered, and directly purified via preparative LCMS (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 60 mL/min) to give the desired product (29 mg, 43%). LCMS for C22H17ClF2N7 (M+H)+: m/z=452.1. Found: 452.0; 1H NMR (300 MHz, DMSO-d6): δ 12.8 (br s, 1H), 8.32-8.23 (m, 1H), 8.11 (s, 1H), 8.06 (s, 1H), 7.65 (s, 1H), 7.46 (s, 1H), 7.36-7.23 (m, 3H), 7.09-7.01 (m, 1H), 6.96 (d, J=8.5 Hz, 1H), 5.09-4.96 (m, 1H), 1.34 (d, J=6.7 Hz, 3H).

後処理

  1. customAlternatively, this reaction
  2. temperatureThe reaction mixture was cooled to room temperature
  3. filtrationfiltered
  4. customdirectly purified via preparative LCMS (XBridge C18 column
  5. washeluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 60 mL/min)

出典と根拠

ORDレコード
ord-4a3e0c9f292846f7ba9aa5d56b5f2b12
出典データセット
uspto-grants-2015_08
特許番号
US09096600B2

反応ノート

読み込み中…