Sodium Bicarbonate → t-Butyl {2-[(4-{3-cyano-5-[(4-isopropylpiperazin-1-yl)methyl]pyridin-2-yl}benzoyl)amino]phenyl}carbamate

HRID 599521노트

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HRID 599521 반응식
[C:1]([O:5][C:6]([NH:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[NH:15][C:16](=[O:32])[C:17]1[CH:22]=[CH:21][C:20](B2OC(C)(C)C(C)(C)O2)=[CH:19][CH:18]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl[C:34]1[N:41]=[CH:40][C:39]([CH2:42][N:43]2[CH2:48][CH2:47][N:46]([CH:49]([CH3:51])[CH3:50])[CH2:45][CH2:44]2)=[CH:38][C:35]=1[C:36]#[N:37].C(=O)([O-])O.[Na+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].COCCOC>[C:36]([C:35]1[C:34]([C:20]2[CH:19]=[CH:18][C:17]([C:16]([NH:15][C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=3[NH:8][C:6](=[O:7])[O:5][C:1]([CH3:3])([CH3:2])[CH3:4])=[O:32])=[CH:22][CH:21]=2)=[N:41][CH:40]=[C:39]([CH2:42][N:43]2[CH2:44][CH2:45][N:46]([CH:49]([CH3:51])[CH3:50])[CH2:47][CH2:48]2)[CH:38]=1)#[N:37]

참가 물질

6

반응물 3

HCID 516892Sodium BicarbonateHCID 59830883N-(2-t-Butoxycarbonylaminophenyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamideHCID 598487902-Chloro-5-[(4-isopropylpiperazin-1-yl)methyl]nicotinonitrile

생성물 1

HCID 86624986t-Butyl {2-[(4-{3-cyano-5-[(4-isopropylpiperazin-1-yl)methyl]pyridin-2-yl}benzoyl)amino]phenyl}carbamate

시약·촉매·용매 2

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 80711,2-Dimethoxyethane용매

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온도
80 °C

실험 절차

1,1′-Bis(diphenylphosphino)ferrocenedichloropalladium (II) chloride (58 mg, 0.072 mmol) was added to a mixture of N-(2-t-butoxycarbonylaminophenyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (626 mg, 1.43 mmol prepared as described in International Patent Publication Number WO03/087057, Method 13, page 60), 2-chloro-5-[(4-isopropylpiperazin-1-yl)methyl]nicotinonitrile (398 mg, 1.43 mmol; see Method 20), saturated aqueous sodium hydrogen carbonate solution (5 ml) and 1,2-dimethoxyethane (10 ml). The mixture was heated at 80° C. for 1 hour then allowed to cool to room temperature and partitioned between dichloromethane (75 ml) and water (50 ml). The aqueous layer was extracted with further dichloromethane (2×75 ml). The combined organics were dried over magnesium sulfate, filtered and then evaporated to dryness. The residue was purified by flash chromatography on silica, eluting with methanol (5-10%) in dichloromethane to afford the title compound as a yellow gum which crystallised on trituration with diethyl ether, (652 mg, 82%).

후처리

  1. temperatureto cool to room temperature
  2. custompartitioned between dichloromethane (75 ml) and water (50 ml)
  3. extractionThe aqueous layer was extracted with further dichloromethane (2×75 ml)
  4. dry with materialThe combined organics were dried over magnesium sulfate
  5. filtrationfiltered
  6. customevaporated to dryness
  7. customThe residue was purified by flash chromatography on silica
  8. washeluting with methanol (5-10%) in dichloromethane

출처 및 근거

ORD 기록
ord-4cd109ca320c45ceb3a072ef146053f8
출처 데이터셋
uspto-grants-2011_03
특허 번호
US07897778B2

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