Potassium Phosphate, Tribasic → 5-(2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroisoquinoline

HRID 2172292

反応式

HRID 2172292 の反応式
Cl.Br[C:3]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:4]=1[CH2:5][CH2:6][NH:7][CH2:8]2.[CH3:13][N:14]1[C:18]([C:19]2[CH:24]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:22]=[CH:21][C:20]=2B(O)O)=[CH:17][CH:16]=[N:15]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>>[CH3:13][N:14]1[C:18]([C:19]2[CH:24]=[C:23]([C:25]([F:26])([F:27])[F:28])[CH:22]=[CH:21][C:20]=2[C:3]2[CH:12]=[CH:11][CH:10]=[C:9]3[C:4]=2[CH2:5][CH2:6][NH:7][CH2:8]3)=[CH:17][CH:16]=[N:15]1

参加物

4

反応物 3

HCID 62657Potassium Phosphate, TribasicHCID 450740035-Bromo-1,2,3,4-tetrahydroisoquinoline hydrochlorideHCID 71258947(2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)boronic acid2 回

生成物 1

HCID 898152865-(2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroisoquinoline

反応条件

温度
90 °C

実験手順

A vial was charged with 5-bromo-1,2,3,4-tetrahydroisoquinoline hydrochloride (ASW Medchem, Brunswick, N.J., 400.42 mg, 1.367 mmol), (2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)boronic acid (Intermediate B, 443 mg, 1.640 mmol), potassium phosphate (1160 mg, 5.47 mmol), and Pd(AmPhos)2Cl2 (Sigma-Aldrich, St. Louis, Mo., 48.4 mg, 0.068 mmol). The vial was flushed with Ar (g), then dioxane (2928 μl) and water (976 μl) were added in sequence. The mixture was heated in a microwave reactor for 30 min at 90° C. After cooling to room temperature, the mixture was diluted with EtOAc, washed with water (and a small amount of brine to break up emulsions, 2×), washed with brine, dried over sodium sulfate, filtered, and concentrated. The residue was taken up in MeOH, then loaded onto a 10 g SCX-2 ion exchange column. The column was eluted with MeOH, then with 2M ammonia in MeOH. The basic filtrate was concentrated, and the residue was chromatographed on a 40 g silica gel column with 0 to 10% MeOH/DCM to provide 5-(2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroisoquinoline as a pale yellow solid. [M+H]+=358.1. 1H NMR (400 MHz, DMSO-d6) δ ppm=7.91-7.80 (m, 2H), 7.56 (d, J=8.0 Hz, 1H), 7.28 (d, J=2.0 Hz, 1H), 7.09-6.95 (m, 2H), 6.84 (dd, J=1.3, 7.4 Hz, 1H), 5.96 (d, J=1.9 Hz, 1H), 3.85 (s, 2H), 3.52 (br. s., 3H), 2.93-2.84 (m, 1H), 2.79-2.67 (m, 1H), 2.48-2.39 (m, 1H), 2.09 (td, J=5.3, 16.7 Hz, 1H).

後処理

  1. customThe vial was flushed with Ar (g)
  2. additiondioxane (2928 μl) and water (976 μl) were added in sequence
  3. temperatureAfter cooling to room temperature
  4. additionthe mixture was diluted with EtOAc
  5. washwashed with water (and a small amount of brine
  6. washwashed with brine
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. washThe column was eluted with MeOH
  11. concentrationThe basic filtrate was concentrated
  12. customthe residue was chromatographed on a 40 g silica gel column with 0 to 10% MeOH/DCM

出典と根拠

ORDレコード
ord-e9ba0b39e7304097bb78aa7b325bc534
出典データセット
uspto-grants-2015_06
特許番号
US09051311B2

関連ノート

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