2,3-Butanediol → Methyl{[5'-isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}[3-pyridin-4-yl-5-(trifluoromethyl)benzyl]carbamate

HRID 17072

반응식

HRID 17072 반응식
[CH3:1][O:2][C:3](=[O:39])[N:4]([CH2:27][C:28]1[CH:33]=[C:32]([C:34]([F:37])([F:36])[F:35])[CH:31]=[C:30](I)[CH:29]=1)[CH2:5][C:6]1[CH:11]=[C:10]([C:12]([F:15])([F:14])[F:13])[CH:9]=[CH:8][C:7]=1[C:16]1[CH:21]=[C:20]([CH:22]([CH3:24])[CH3:23])[CH:19]=[CH:18][C:17]=1[O:25][CH3:26].[N:40]1[CH:45]=[CH:44][C:43](B(O)O)=[CH:42][CH:41]=1.CC(O)C(O)C.C([O-])([O-])=O.[Na+].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O.C(O)C>[CH3:1][O:2][C:3](=[O:39])[N:4]([CH2:5][C:6]1[CH:11]=[C:10]([C:12]([F:13])([F:14])[F:15])[CH:9]=[CH:8][C:7]=1[C:16]1[CH:21]=[C:20]([CH:22]([CH3:23])[CH3:24])[CH:19]=[CH:18][C:17]=1[O:25][CH3:26])[CH2:27][C:28]1[CH:33]=[C:32]([C:34]([F:37])([F:36])[F:35])[CH:31]=[C:30]([C:43]2[CH:44]=[CH:45][N:40]=[CH:41][CH:42]=2)[CH:29]=1

참가 물질

8

반응물 4

HCID 2622,3-ButanediolHCID 10340Sodium CarbonateHCID 2734379(Pyridin-4-yl)boronic acidHCID 86615395Methyl[3-iodo-5-(trifluoromethyl)benzyl]{[5'-isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}carbamate

생성물 1

HCID 11657359Methyl{[5'-isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}[3-pyridin-4-yl-5-(trifluoromethyl)benzyl]carbamate

시약·촉매·용매 3

HCID 178418397HCID 178418397, 화합물촉매HCID 702Ethanol용매HCID 962Water용매

실험 절차

Methyl[3-iodo-5-(trifluoromethyl)benzyl]{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}carbamate (Example 119, 20 mg, 0.03 mmol) and pyridine-4-boronic acid (4.6 mg, 0.04 mmol) were placed in a microwave tube in a microwave tube, and dissolved with dimethyl ethylene glycol (170 μL). Next, 2M Na2CO3 (38 μL), ethanol (42 μL), and water (56 μL) were added. The solution was degassed with nitrogen for 2 minutes. Pd(PPh3)4 (3.5 mg, 0.003 mmol) was added and the solution was degassed with nitrogen again for 2 minutes. The solution was sealed and placed in a microwave reactor. The wattage was set for 60 W until the temperature reached 150° C. and then the temperature was held at 150° C. for twenty minutes. The mixture was then cooled to room temperature, poured into H2O (10 mL), and extracted with EtOAc (30 mL). The organic layer was washed with brine (10 mL), dried over Na2SO4, filtered, and concentrated. Purification by flash chromatography with 5% to 80% EtOAc/hexanes afforded methyl{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl)}[3-pyridin-4-yl-5-(trifluoromethyl)benzyl]carbamate. Rf=0.40 (75% EtOAc/hexanes). LCMS=617.3 (M+1)+. 1H NMR (C6D6, 500 MHz, 70° C.) δ 8.54 (broad singlet, 2H), 7.70 (s, 1H), 7.51 (s, 1H), 7.38 (s, 1H), 7.35 (d, J=8.0, 1H), 7.28 (s, 1H), 7.06 (d, J=8.0, 1H), 7.02 (dd, J=2.0 Hz, 8.5, 1H), 6.89 (m, 2H), 6.83 (d, J=2.0, 1H), 6.58 (d, J=8.5, 1H), 4.45 (broad singlet, 2H), 4.13 (broad singlet, 2H), 3.38 (s, 3H), 3.23 (s, 3H), 2.65 (m, 1H), 1.12 (d, J=7.0 Hz, 6H).

후처리

  1. customThe solution was degassed with nitrogen for 2 minutes
  2. customthe solution was degassed with nitrogen again for 2 minutes
  3. customThe solution was sealed
  4. customplaced in a microwave reactor
  5. customreached 150° C.
  6. waitthe temperature was held at 150° C. for twenty minutes
  7. additionpoured into H2O (10 mL)
  8. extractionextracted with EtOAc (30 mL)
  9. washThe organic layer was washed with brine (10 mL)
  10. dry with materialdried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customPurification by flash chromatography with 5% to 80% EtOAc/hexanes
  14. customafforded methyl{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl)}[3-pyridin-4-yl-5-(trifluoromethyl)benzyl]carbamate

출처 및 근거

ORD 기록
ord-0d12ea11912e475999691120cddbf015
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07737295B2

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