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

HRID 539374

반응식

HRID 539374 반응식
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

참가 물질

8

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 178479786HCID 178479786, 화합물촉매HCID 6344Dichloromethane용매

반응 조건

온도
90 °C

실험 절차

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]+.

후처리

  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

출처 및 근거

ORD 기록
ord-d49f2e4c4f404a8283f239a9373def63
출처 데이터셋
uspto-grants-2014_10
특허 번호
US08865911B2

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