Potassium Carbonate → tert-butyl 2-[3-(bis(tert-butoxycarbonyl)amino)-6-(1-tert-butoxycarbonyl-3,6-dihydro-2H-pyridin-4-yl)pyrazin-2-yl]benzimidazole-1-carboxylate

HRID 1959408노트

반응식

HRID 1959408 반응식
[C:1]([O:5][C:6]([N:8]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[C:9]1[C:10]([C:16]2[N:20]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[C:19]3[CH:28]=[CH:29][CH:30]=[CH:31][C:18]=3[N:17]=2)=[N:11][C:12](Br)=[CH:13][N:14]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CC1(C)C(C)(C)OB([C:47]2[CH2:48][CH2:49][N:50]([C:53]([O:55][C:56]([CH3:59])([CH3:58])[CH3:57])=[O:54])[CH2:51][CH:52]=2)O1.C(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)(C)C.C([O-])([O-])=O.[K+].[K+]>C1(C)C=CC=CC=1.O.Cl[Pd]Cl>[C:1]([O:5][C:6]([N:8]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[C:9]1[C:10]([C:16]2[N:20]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[C:19]3[CH:28]=[CH:29][CH:30]=[CH:31][C:18]=3[N:17]=2)=[N:11][C:12]([C:47]2[CH2:52][CH2:51][N:50]([C:53]([O:55][C:56]([CH3:59])([CH3:58])[CH3:57])=[O:54])[CH2:49][CH:48]=2)=[CH:13][N:14]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

참가 물질

8

반응물 4

HCID 11430Potassium CarbonateHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 11714598(4-(N,N-Dimethylamino)phenyl)di-tert-butyl phosphineHCID 86662069Tert-butyl 2-(3-(bis(tert-butoxycarbonyl)amino)-6-bromopyrazin-2-yl)-1H-benzo[d]imidazole-1-carboxylate

생성물 1

HCID 66745281tert-butyl 2-[3-(bis(tert-butoxycarbonyl)amino)-6-(1-tert-butoxycarbonyl-3,6-dihydro-2H-pyridin-4-yl)pyrazin-2-yl]benzimidazole-1-carboxylate수율 85.6%

시약·촉매·용매 3

HCID 24290Palladium Chloride촉매HCID 962Water용매HCID 1140Toluene용매

실험 절차

A mixture of tert-butyl 2-[3-[bis(tert-butoxycarbonyl)amino]-6-bromo-pyrazin-2-yl]benzimidazole-1-carboxylate (1.7068 g, 1.734 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylate (643.5 mg, 2.081 mmol), 4-ditert-butylphosphanyl-N,N-dimethyl-aniline; dichloropalladium (12.28 mg, 0.01734 mmol) and K2CO3 (479.3 mg, 3.468 mmol) in toluene (9.216 mL) and water (1.024 mL) was heated to 100° C. for 16 hours. The reaction mixture was allowed to cool to RT and partitioned between DCM and water. The organic layer was washed with 1M NaOH solution, dried (Na2SO4), filtered and concentrated in vacuo to give a brown oil. This was purified by column chromatography (ISCO Companion™, 40 g column, 0-20% EtOAc/Petrol) to afford the title compound as a yellow oil (1.028 g, 60% Yield). MS (ES+) 693.38

후처리

  1. custompartitioned between DCM and water
  2. washThe organic layer was washed with 1M NaOH solution
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto give a brown oil
  7. customThis was purified by column chromatography (ISCO Companion™, 40 g column, 0-20% EtOAc/Petrol)

출처 및 근거

ORD 기록
ord-9d621c2ba32c4a4f9255cb67f0384693
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08410112B2

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