Adenine → N6-(N-methyl-2-pyrrolidin-ylidene)-9-[(1RS,4SR)-4-hydroxy-cyclopent-2-en-1-yl]adenine

HRID 1780756노트

반응식

HRID 1780756 반응식
P(OC(C)C)(OC(C)C)OC(C)C.C([Li])CCC.CCCCCC.[CH3:25][N:26]1[CH2:30][CH2:29][CH2:28][C:27]1=[N:31][C:32]1[N:40]=[CH:39][N:38]=[C:37]2[C:33]=1[NH:34][CH:35]=[N:36]2.N1C(N)=C2C(N=CN2)=NC=1.[O:51]1[C:53]2[CH2:54][CH2:55][CH2:56][C:52]1=2>O1CCCC1.CC(O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CN1CCCC1=O.CS(C)=O>[CH3:25][N:26]1[CH2:30][CH2:29][CH2:28][C:27]1=[N:31][C:32]1[N:40]=[CH:39][N:38]=[C:37]2[C:33]=1[N:34]=[CH:35][N:36]2[CH:55]1[CH2:56][CH:52]([OH:51])[CH:53]=[CH:54]1

참가 물질

12

반응물 6

HCID 190AdenineHCID 8058HexaneHCID 8304Triisopropyl phosphiteHCID 19047329N6-(N-methyl-pyrrolidin-ylidene)adenineHCID 22121731HCID 22121731, 화합물HCID 178418339Butyllithium

생성물 1

HCID 67878693N6-(N-methyl-2-pyrrolidin-ylidene)-9-[(1RS,4SR)-4-hydroxy-cyclopent-2-en-1-yl]adenine수율 27.1%

시약·촉매·용매 5

HCID 167845palladium(II) acetate촉매HCID 679Dimethyl Sulfoxide용매HCID 3776Isopropanol용매HCID 8028Tetrahydrofuran용매2회HCID 13387N-methyl-2-pyrrolidone용매

실험 절차

224 mg (1 mmol) of palladium(II) acetate, 2.5 ml (10 mmol) of triisopropyl phosphite and 1.5 ml of 1.6 molar n-butyllithium solution in n-hexane (2 mmol) are brought together in 40 ml of dry tetrahydrofuran at 0° C. under inert nitrogen gas and the mixture is stirred. After addition of 30 ml of dry dimethylsulfoxide, 4.32 g (20 mmol) of N6 -(N-methyl-pyrrolidin-ylidene)adenine (prepared by reaction of adenine with the diethyl acetal of N-methyl-pyrrolid-2-one in 2-propanol; beige powder, melting point: 248°-251° C.) are added; a solution of 1.64 g (20 mmol) of epoxycyclopentene in 20 ml of dry tetrahydrofuran is then added dropwise in the course of one hour. The solution is stirred at room temperature for 12 hours and then concentrated and the residue is chromatographed over silica gel (methylene chloride/methanol 9/1). 1.62 g (27% of theory) of N6 -(N-methyl-2-pyrrolidin-ylidene)-9-[(1RS,4SR)-4-hydroxy-cyclopent-2-en-1-yl]adenine of melting point 135°-138° C. are obtained in a regiospecific manner. 1H NMR (270 MHz, d6 -DMSO), δ[ppm]: 8.42 (s, 1H), 8.16 (s, 1H), 6.20 (m, 1H), 6.00 (m, 1H), 5.50 (m, 1H), 5.46 (d, 1H), 4.73 (m, 1H), 3.50 (t, 2H), 3.04 (s, 3H), 2.90 (m, 1H), 2.85 (t, 2H), 1.97 (p, 2H), 1.74 (m, 1H). N6 -(N-Methyl-2-pyrrolidin-ylidene)-9-(cyclopent-1-en-3-on-1-yl)adenine of melting point 200°-205° C. is isolated as a by-product (20 mg, 0.3% of theory). 1H NMR (270 MHz, CDCl3), δ[ppm]: 8.64 (s, 1H), 8.13 (s, 1H), 7.19 (m, 1H), 3.53 (t, 2H), 3.34 (m, 2H), 3.20 (s, 3H), 3.07 (t, 2H), 2.65 (m, 2H), 2.10 (p, 2H).

후처리

  1. additionbeige powder, melting point: 248°-251° C.) are added
  2. stirringThe solution is stirred at room temperature for 12 hours
  3. concentrationconcentrated
  4. customthe residue is chromatographed over silica gel (methylene chloride/methanol 9/1)

출처 및 근거

ORD 기록
ord-748dfcba98824a7cb055ff27a78ee47d
출처 데이터셋
uspto-grants-1997_05
특허 번호
US05631259

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