Sodium Carbonate → 4-{2-[4-(1-Tert-butoxycarbonylamino-cyclobutyl)-phenyl]-3-phenyl-imidazo[1,2-a]pyridin-7-yl}-pyrazole-1-carboxylic acid tert-butyl ester

HRID 872319노트

반응식

HRID 872319 반응식
[C:1]([O:5][C:6](=[O:34])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[N:19]=[C:20]4[CH:25]=[C:24](Br)[CH:23]=[CH:22][N:21]4[C:27]=3[C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[C:35]([O:39][C:40]([N:42]1[CH:46]=[C:45](B(O)O)[CH:44]=[N:43]1)=[O:41])([CH3:38])([CH3:37])[CH3:36].C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.O.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].Cl[Pd]Cl>[C:35]([O:39][C:40]([N:42]1[CH:46]=[C:45]([C:24]2[CH:23]=[CH:22][N:21]3[C:27]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)=[C:18]([C:15]4[CH:16]=[CH:17][C:12]([C:8]5([NH:7][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:34])[CH2:11][CH2:10][CH2:9]5)=[CH:13][CH:14]=4)[N:19]=[C:20]3[CH:25]=2)[CH:44]=[N:43]1)=[O:41])([CH3:38])([CH3:36])[CH3:37]

참가 물질

7

반응물 3

HCID 10340Sodium CarbonateHCID 441186751-tert-Butoxycarbonyl-1H-pyrazole-4-boronic acidHCID 66665545{1-[4-(7-Bromo-3-phenyl-imidazo[1,2-a]pyridin-2-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester

생성물 1

HCID 666657094-{2-[4-(1-Tert-butoxycarbonylamino-cyclobutyl)-phenyl]-3-phenyl-imidazo[1,2-a]pyridin-7-yl}-pyrazole-1-carboxylic acid tert-butyl ester수율 104.4%

시약·촉매·용매 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 962Water용매HCID 312751,4-Dioxane용매

반응 조건

온도
105 °C

실험 절차

A mixture of {1-[4-(7-bromo-3-phenyl-imidazo[1,2-a]pyridin-2-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester (150 mg), [1-(tert-butoxycarbonyl)-1H-pyrazol-4-yl]boronic acid (123 mg), 1,1′-bis(diphenylphosphino)ferrocene-dichloropalladium(II) (24 mg) and sodium carbonate (92 mg) in dioxane (3.1 mL) and water (0.4 mL) was degassed, placed under an argon atmosphere and heated at 105° C. under microwave irradiation for 30 minutes. On cooling, a further portion of catalyst was added (24 mg) and the mixture heated for a further 30 minutes under microwave irradiation. On cooling, the reaction was partitioned between aqueous ammonium chloride solution and DCM and the organic phase washed with brine, dried and concentrated in vacuo to give the crude title compound (183 mg) which was used in the next step (deprotection of both Boc groups under the standard conditions given in Example 1.0) without further purification.

후처리

  1. customwas degassed
  2. temperatureOn cooling
  3. additiona further portion of catalyst was added (24 mg)
  4. temperaturethe mixture heated for a further 30 minutes under microwave irradiation
  5. temperatureOn cooling
  6. customthe reaction was partitioned between aqueous ammonium chloride solution and DCM
  7. washthe organic phase washed with brine
  8. customdried
  9. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-1098d0592ea24393842c23ba07c5aa30
출처 데이터셋
uspto-grants-2015_03
특허 번호
US08975265B2

반응 노트

불러오는 중…