2-Methyltetrahydrofuran → 6'-(5-Chloropyridin-3-yl)-5''-methyl-3'H-dispiro[cyclobutane-1,2'-indene-1',2''-imidazol]-4''-amine

HRID 539374

反応式

HRID 539374 の反応式
CC([PH+](C(C)(C)C)CCCS([O-])(=O)=O)(C)C.[Cl:17][C:18]1[CH:19]=[C:20](B(O)O)[CH:21]=[N:22][CH:23]=1.Br[C:28]1[CH:45]=[C:44]2[C:31]([CH2:32][C:33]3([C:37]42[N:41]=[C:40]([NH2:42])[C:39]([CH3:43])=[N:38]4)[CH2:36][CH2:35][CH2:34]3)=[CH:30][CH:29]=1.CC1CCCO1.C([O-])([O-])=O.[K+].[K+]>C(Cl)Cl.[Na+].[Na+].Cl[Pd+2](Cl)(Cl)Cl>[Cl:17][C:18]1[CH:19]=[C:20]([C:28]2[CH:45]=[C:44]3[C:31]([CH2:32][C:33]4([C:37]53[N:41]=[C:40]([NH2:42])[C:39]([CH3:43])=[N:38]5)[CH2:36][CH2:35][CH2:34]4)=[CH:30][CH:29]=2)[CH:21]=[N:22][CH:23]=1

参加物

8

反応物 5

HCID 73012-MethyltetrahydrofuranHCID 11430Potassium CarbonateHCID 201118775-Chloropyridine-3-boronic acidHCID 249491873-(Di-tert-butylphosphonium)propane sulfonateHCID 573866666'-Bromo-5''-methyl-3'H-dispiro[cyclobutane-1,2'-indene-1',2''-imidazol]-4''-amine

生成物 1

HCID 573866676'-(5-Chloropyridin-3-yl)-5''-methyl-3'H-dispiro[cyclobutane-1,2'-indene-1',2''-imidazol]-4''-amine収率 77%

試薬・触媒・溶媒 2

HCID 178479786HCID 178479786、化合物触媒HCID 6344Dichloromethane溶媒

反応条件

温度
90 °C

実験手順

Sodium tetrachloropalladate (II) (2.77 mg, 9.43 μmol), 3-(di-tert-butylphosphonium)propane sulfonate (5.06 mg, 0.02 mmol), 5-chloropyridin-3-ylboronic acid (40.6 mg, 0.25 mmol) and 6′-bromo-5″-methyl-3′H-dispiro[cyclobutane-1,2′-indene-1′,2″-imidazol]-4″-amine (Example 54, 60 mg, 0.19 mmol), was added to a vial. 2-Methyl-tetrahydrofuran (1 mL) and 2 M aq. K2CO3 (0.283 mL, 0.57 mmol) was added and the mixture was degassed by bubbling N2 (g). The vial was sealed and heated in a microwave reactor at 90° C. for 30 min. EtOAc (5 mL) and water (5 mL) were added and the phases were separated. The aq phase was extracted with EtOAc and the combined organic layers were dried over MgSO4, filtered and concentrated in vacuo. Purification by flash chromatography using a gradient of 0-10% MeOH, containing 1.2% 7M NH3 in MeOH, in DCM, afforded 51 mg of the title compound (77% yield). 1H NMR (500 MHz, DMSO-d6) δ ppm 1.62 (m, 4 H) 1.83 (d, 1 H) 2.16 (s, 1 H) 2.21 (s, 3 H) 3.23 (d, 2 H) 6.60 (s, 2 H) 6.94 (d, 1 H) 7.43 (d, 1 H) 7.58 (dd, 1 H) 8.10 (t, 1 H) 8.57 (d, 1 H) 8.71 (d, 1 H); MS (ES+) m/z 351 [M+H]+.

後処理

  1. customthe mixture was degassed
  2. customby bubbling N2 (g)
  3. customThe vial was sealed
  4. additionEtOAc (5 mL) and water (5 mL) were added
  5. customthe phases were separated
  6. extractionThe aq phase was extracted with EtOAc
  7. dry with materialthe combined organic layers were dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customPurification by flash chromatography
  11. additioncontaining 1.2% 7M NH3 in MeOH

出典と根拠

ORDレコード
ord-d49f2e4c4f404a8283f239a9373def63
出典データセット
uspto-grants-2014_10
特許番号
US08865911B2

関連ノート

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