Cesium carbonate → 2-(5-chloro-2-nitrophenylamino)-6-(pyridin-4-yl)-9-(tetrahydro-2H-pyran-4-yl)-7H-purin-8(9H)-one

HRID 2074159노트

반응식

HRID 2074159 반응식
[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([NH:6][C:7](=[O:17])[N:8]2[CH:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)=[C:4]([C:18]2[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=2)[N:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.Br[C:77]1[CH:82]=[C:81]([Cl:83])[CH:80]=[CH:79][C:78]=1[N+:84]([O-:86])=[O:85]>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2].CS(C)=O>[Cl:83][C:81]1[CH:80]=[CH:79][C:78]([N+:84]([O-:86])=[O:85])=[C:77]([NH:1][C:2]2[N:10]=[C:9]3[C:5]([NH:6][C:7](=[O:17])[N:8]3[CH:11]3[CH2:12][CH2:13][O:14][CH2:15][CH2:16]3)=[C:4]([C:18]3[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=3)[N:3]=2)[CH:82]=1

참가 물질

8

반응물 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 98561242-Bromo-4-chloro-1-nitrobenzeneHCID 576126402-amino-6-(pyridin-4-yl)-9-(tetrahydro-2H-pyran-4-yl)-7H-purin-8(9H)-one

생성물 1

HCID 576127192-(5-chloro-2-nitrophenylamino)-6-(pyridin-4-yl)-9-(tetrahydro-2H-pyran-4-yl)-7H-purin-8(9H)-one수율 11%

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매HCID 679Dimethyl Sulfoxide용매HCID 1140Toluene용매

반응 조건

온도
170 °C

실험 절차

To an oven-dried vial was added 2-amino-6-(pyridin-4-yl)-9-(tetrahydro-2H-pyran-4-yl)-7H-purin-8(9H)-one (68 mg, 0.22 mmol, 1 equiv.) in anhydrous toluene (1 mL), then freshly grounded cesium carbonate (99.4 mg, 0.31 mmol, 1.4 equiv.) with stirring at room temperature under Ar. After 20 min, Pd(OAc)2 (15 mg, 0.02 mmol, 0.1 equiv.), racemic BINAP (20.5 mg, 0.03 mmol, 0.15 equiv.) and 1-bromo-5-chloro-2-nitrobenzene (WO 02/053545 A1) (67.6 mg, 0.29 mmol, 1.3 equiv.) were added as solids, followed by anhydrous DMSO (1 mL). The vial was purged with Ar for 3 min, then closed and heated in a microwave oven at 170° C. for 45 min. The reaction mixture was cooled to room temperature, diluted with ethyl acetate/methylene chloride, filtered through a Nylon 0.45 μm filter, and the filtrate was concentrated in vacuo. The resulting residue was purified using preparative TLC (silica gel, 7.5% methanol in methylene chloride) to give the desired product as a brown solid (11 mg, 11% yield). 1H NMR (300 MHz, CDCl3+CD3OD) δ, ppm: 9.13 (s, 1H), 8.63 (br m, 2H), 8.13 (d, J=8.9 Hz, 1H), 7.83 (br m, 2H), 6.91 (d, J=8.6 Hz, 1H), 4.70-4.50 (m, 1H), 4.10-4.03 (m, 2H), 3.51-3.43 (m, 2H), 2.68-2.65 (m, 2H), 1.71-1.66 (m, 2H); MS (EI) m/z 468.4 (MH)+.

후처리

  1. customThe vial was purged with Ar for 3 min
  2. customclosed
  3. temperatureThe reaction mixture was cooled to room temperature
  4. additiondiluted with ethyl acetate/methylene chloride
  5. filtrationfiltered through a Nylon 0.45 μm
  6. filtrationfilter
  7. concentrationthe filtrate was concentrated in vacuo
  8. customThe resulting residue was purified

출처 및 근거

ORD 기록
ord-1d226e9874514b37a9d0950ceb6ef3dc
출처 데이터셋
uspto-grants-2011_04
특허 번호
US07919490B2

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