Methylhydrazine → PF-04981517

HRID 72702노트

반응식

HRID 72702 반응식
ClC1C(C(C2[CH:11]=[N:12][N:13](C)C=2C2C=CC(C)=CC=2)=O)=C(Cl)N=CN=1.C(N(CC)C(C)C)(C)C.N1CC[C@H](N2CCCCC2)C1.Cl[C:45]1[C:50]([C:51]([C:53]2[CH:54]=[N:55][N:56]([CH3:65])[C:57]=2[C:58]2[CH:63]=[CH:62][C:61]([CH3:64])=[CH:60][CH:59]=2)=O)=[C:49]([N:66]2[CH2:70][CH2:69][C@H:68]([N:71]3[CH2:76][CH2:75][CH2:74][CH2:73][CH2:72]3)[CH2:67]2)[N:48]=[CH:47][N:46]=1.CNN>C(#N)C>[CH3:11][N:12]1[C:45]2=[N:46][CH:47]=[N:48][C:49]([N:66]3[CH2:70][CH2:69][C@H:68]([N:71]4[CH2:72][CH2:73][CH2:74][CH2:75][CH2:76]4)[CH2:67]3)=[C:50]2[C:51]([C:53]2[CH:54]=[N:55][N:56]([CH3:65])[C:57]=2[C:58]2[CH:59]=[CH:60][C:61]([CH3:64])=[CH:62][CH:63]=2)=[N:13]1

참가 물질

7

반응물 5

HCID 6061MethylhydrazineHCID 81531DiisopropylethylamineHCID 71763141-(3S)-3-Pyrrolidinyl-piperidineHCID 86712558(4,6-dichloropyrimidin-5-yl)[1-methyl-5-(4-methylphenyl)-1H-pyrazol-4-yl]methanoneHCID 86712560{4-chloro-6-[(3S)-3-(piperidin-1-yl)pyrrolidin-1-yl]pyrimidin-5-yl}[1-methyl-5-(4-methylphenyl)-1H-pyrazol-4-yl]methanone

생성물 1

HCID 71315139PF-04981517수율 90%

시약·촉매·용매 1

HCID 6342Acetonitrile용매2회

실험 절차

To a mixture of (4,6-dichloropyrimidin-5-yl)[1-methyl-5-(4-methylphenyl)-1H-pyrazol-4-yl]methanone (C5) (7.3 g, 21 mmol) and N,N-diisopropylethylamine (13.56 g, 104.9 mmol) in acetonitrile (100 mL) was added 1-[(3S)-pyrrolidin-3-yl]piperidine (4.8 g, 31 mmol), and the resulting reaction mixture was stirred at room temperature for 3 hours. To this solution of {4-chloro-6-[(3S)-3-(piperidin-1-yl)pyrrolidin-1-yl]pyrimidin-5-yl}[1-methyl-5-(4-methylphenyl)-1H-pyrazol-4-yl]methanone (C7) was added drop-wise a solution of methylhydrazine (12.1 g, 262 mol) in acetonitrile (20 mL). After being stirred overnight at room temperature, the reaction mixture was concentrated in vacuo and partitioned between dichloromethane (100 mL) and water (100 mL). The aqueous layer was extracted with dichloromethane (2×100 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated; purification via silica gel chromatography (Gradient: 10% to 50% ethyl acetate in petroleum ether) afforded the product as a white solid. Yield: 8.64 g, 18.9 mmol, 90% yield. LCMS m/z 457.3 (M+1). 1H NMR (400 MHz, CDCl3) δ 1.39-1.49 (br m, 2H), 1.53-1.73 and 2.00-2.25 (br multiplets, presumed 8H), 2.31 (s, 3H), 2.32-2.45 (br m, 2H), 2.56-2.68 (br m, 1H), 2.90-3.16 (v br m, 1H), 3.26-3.78 (br m, 3H), 3.87 (s, 3H), 4.00 (s, 3H), 7.16 (br AB quartet, JAB=8 Hz, ΔνAB=26 Hz, 4H), 7.66 (s, 1H), 8.29 (s, 1H).

후처리

  1. customthe resulting reaction mixture
  2. stirringAfter being stirred overnight at room temperature
  3. concentrationthe reaction mixture was concentrated in vacuo
  4. custompartitioned between dichloromethane (100 mL) and water (100 mL)
  5. extractionThe aqueous layer was extracted with dichloromethane (2×100 mL)
  6. dry with materialThe combined organic layers were dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. custompurification via silica gel chromatography (Gradient: 10% to 50% ethyl acetate in petroleum ether)

출처 및 근거

ORD 기록
ord-4460796c9c5844aeb4eff27a26d42044
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08829010B2

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