1,2-Dimethoxyethane → tert-butyl N-[2-[([4-[3,5-dimethyl-4-(propan-2-yloxy)phenyl]-1-(oxan-2-yl)-1H-pyrrol-3-yl]methyl)(methyl)amino]ethyl]carbamate

HRID 526749

反応式

HRID 526749 の反応式
I[C:2]1[C:6]([CH2:7][N:8]([CH3:19])[CH2:9][CH2:10][NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[CH:5][N:4]([CH:20]2[CH2:25][CH2:24][CH2:23][CH2:22][O:21]2)N=1.[CH3:26][C:27]1[CH:28]=[C:29](B(O)O)[CH:30]=[C:31]([CH3:37])[C:32]=1[O:33][CH:34]([CH3:36])[CH3:35].[O-]P([O-])([O-])=O.[K+].[K+].[K+].[CH3:49]OCCOC>O.ClCCl.CC(P(C(C)(C)C)[C]1[CH][CH][CH][CH]1)(C)C.CC(P(C(C)(C)C)[C]1[CH][CH][CH][CH]1)(C)C.Cl[Pd]Cl.[Fe]>[CH3:26][C:27]1[CH:28]=[C:29]([C:2]2[C:6]([CH2:7][N:8]([CH3:19])[CH2:9][CH2:10][NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[CH:5][N:4]([CH:20]3[CH2:25][CH2:24][CH2:23][CH2:22][O:21]3)[CH:49]=2)[CH:30]=[C:31]([CH3:37])[C:32]=1[O:33][CH:34]([CH3:36])[CH3:35]

参加物

8

反応物 4

HCID 80711,2-DimethoxyethaneHCID 62657Potassium Phosphate, TribasicHCID 16217511{3,5-Dimethyl-4-[(propan-2-yl)oxy]phenyl}boronic acidHCID 90433946HCID 90433946、化合物

生成物 1

HCID 117666078tert-butyl N-[2-[([4-[3,5-dimethyl-4-(propan-2-yloxy)phenyl]-1-(oxan-2-yl)-1H-pyrrol-3-yl]methyl)(methyl)amino]ethyl]carbamate

試薬・触媒・溶媒 3

HCID 178454869HCID 178454869、化合物触媒HCID 962Water溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
85 °C

実験手順

A mixture of tert-butyl N-[2-([[3-iodo-1-(oxan-2-yl)-1H-pyrazol-4-yl]methyl](methyl)amino)ethyl]carbamate (500 mg, 1.08 mmol, 1.00 equiv), [3,5-dimethyl-4-(propan-2-yloxy)phenyl]boronic acid (672 mg, 3.23 mmol, 3.00 equiv), [1,1′-Bis(di-tert-butylphosphino)ferrocene]dichloropalladium(II) (70 mg, 0.11 mmol, 0.10 equiv) and K3PO4 (680 mg, 3.21 mmol, 2.98 equiv) in ethylene glycol dimethyl ether (6 mL) and water (0.2 mL) was stirred overnight at 85° C. The reaction was cooled to room temperature, diluted with 30 mL of dichloromethane and washed with 3×20 mL of brine. The organic layer was dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was purified on a silica gel column eluted with 0-10% of MeOH in CH2Cl2 to give 650 mg of tert-butyl N-[2-[([4-[3,5-dimethyl-4-(propan-2-yloxy)phenyl]-1-(oxan-2-yl)-1H-pyrrol-3-yl]methyl)(methyl)amino]ethyl]carbamate as a yellow oil. 1H-NMR (300 MHz, DMSO-d6): δ 7.81 (s, 1H), 7.46 (s, 1H), 7.42 (d, J=4.8 Hz, 1H), 5.40-5.30 (m, 1H), 4.21-4.09 (m, 1H), 4.01-3.88 (m, 2H), 3.47-3.41 (m, 1H), 3.35-3.30 (m, 1H), 3.10 (s, 1H), 2.40-2.32 (m, 1H), 2.18-2.08 (s, 9H), 2.08 (s, 1H), 1.61-1.50 (m, 1H), 1.37-1.35 (m, 4H), 1.21 (s, 15H), 1.05-1.03 (m, 2H) ppm. LCMS (method A, ESI): RT=1.37 min, m/z=501.0 [M+H]+.

後処理

  1. temperatureThe reaction was cooled to room temperature
  2. washwashed with 3×20 mL of brine
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. concentrationconcentrated under vacuum
  5. customThe residue was purified on a silica gel column
  6. washeluted with 0-10% of MeOH in CH2Cl2

出典と根拠

ORDレコード
ord-47e1e0d9bcaa4e89a93bf5a403d813a9
出典データセット
uspto-grants-2016_05
特許番号
US09346761B2

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