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Dichloromethane → 3-(5-(2-chloropyrimidin-4-yl)-2-cyclopropyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-4-yl)-2-fluoroaniline

HRID 535749
ノート
印刷プレビュー

反応式

HRID 535749 の反応式
Br[C:2]1[N:3]=[C:4]([CH:22]2[CH2:24][CH2:23]2)[N:5]([CH2:14][O:15][CH2:16][CH2:17][Si:18]([CH3:21])([CH3:20])[CH3:19])[C:6]=1[C:7]1[CH:12]=[CH:11][N:10]=[C:9]([Cl:13])[N:8]=1.[F:25][C:26]1[C:32](B2OC(C)(C)C(C)(C)O2)=[CH:31][CH:30]=[CH:29][C:27]=1[NH2:28].C(=O)([O-])[O-].[Na+].[Na+].C(Cl)Cl>[NH4+].[Cl-].COCCOC>[Cl:13][C:9]1[N:8]=[C:7]([C:6]2[N:5]([CH2:14][O:15][CH2:16][CH2:17][Si:18]([CH3:21])([CH3:20])[CH3:19])[C:4]([CH:22]3[CH2:24][CH2:23]3)=[N:3][C:2]=2[C:32]2[C:26]([F:25])=[C:27]([CH:29]=[CH:30][CH:31]=2)[NH2:28])[CH:12]=[CH:11][N:10]=1
参加物実験手順後処理出典と根拠反応ノート

参加物

7

反応物 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 581644342-Fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)anilineHCID 866514084-(4-bromo-2-cyclopropyl-1-((2-(trimethylsilyl)ethoxy) methyl)-1H-imidazol-5-yl)-2-chloropyrimidine

生成物 1

HCID 866514093-(5-(2-chloropyrimidin-4-yl)-2-cyclopropyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-4-yl)-2-fluoroaniline
収率 38%

試薬・触媒・溶媒 2

HCID 80711,2-Dimethoxyethane溶媒HCID 25517Ammonium Chloride溶媒

実験手順

To a microwave vial with stir bar was added 4-(4-bromo-2-cyclopropyl-1-((2-(trimethylsilyl)ethoxy) methyl)-1H-imidazol-5-yl)-2-chloropyrimidine (I-1a, step 5, 0.55 g, 1.3 mmol), 2-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (0.61 g, 2.6 mmol), 2.0 M aqueous sodium carbonate solution (3.2 mL, 6.4 mmol) and DME (6.4 mL). The resulting mixture was sparged with nitrogen followed by the addition of PdCl2(dppf).DCM adduct (0.052 g, 0.06 mmol). The reaction was sealed and irradiated in microwave reactor for 20 minutes at 120° C. The reaction mixture was diluted with a saturated aqueous NH4Cl solution and extracted with EtOAc. The organic phase was washed with water, brine, dried (Na2SO4), filtered, concentrated, and adsorbed onto silica gel. Purification by flash chromatography (SiO2, 0-100% EtOAc in heptane) yielded 3-(5-(2-chloropyrimidin-4-yl)-2-cyclopropyl-1-((2-(trimethylsilyl)ethoxy) methyl)-1H-imidazol-4-yl)-2-fluoroaniline (223 mg, 0.48 mmol, 38%) as a viscous yellow oil: LCMS (m/z) 460.1 (MH+), tR=0.95 minute.

後処理

  1. customThe resulting mixture was sparged with nitrogen
  2. additionfollowed by the addition of PdCl2(dppf)
  3. customThe reaction was sealed
  4. customirradiated in microwave reactor for 20 minutes at 120° C
  5. extractionextracted with EtOAc
  6. washThe organic phase was washed with water, brine
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customPurification by flash chromatography (SiO2, 0-100% EtOAc in heptane)

出典と根拠

ORDレコード
ord-2fa0a71f3dba4becbbae17986f0760ff
出典データセット
uspto-grants-2014_10
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08859548B2

反応ノート

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