Triethylamine → ethyl 3-amino-5({[(1S)-2-(dimethylamino)-1-phenylethyl]hydroxy}carbonyl)-6,6-dimethyl-5,6-dihydropyrrolo[3,4-c]pyrazole-1(4H)-carboxylate

HRID 41363노트

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HRID 41363 반응식
[CH3:1][N:2]([CH3:12])[CH2:3][C@H:4]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[OH:5].C(N(CC)CC)C.Cl[C:21](OC1C=CC([N+]([O-])=O)=CC=1)=[O:22].CCN(C(C)C)C(C)C.Cl.Cl.[NH2:44][C:45]1[C:46]2[CH2:57][NH:56][C:55]([CH3:59])([CH3:58])[C:47]=2[N:48]([C:50]([O:52][CH2:53][CH3:54])=[O:51])[N:49]=1>ClCCCl.ClCCl>[NH2:44][C:45]1[C:46]2[CH2:57][N:56]([C:21]([O:5][C@@H:4]([C:6]3[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=3)[CH2:3][N:2]([CH3:12])[CH3:1])=[O:22])[C:55]([CH3:58])([CH3:59])[C:47]=2[N:48]([C:50]([O:52][CH2:53][CH3:54])=[O:51])[N:49]=1

참가 물질

8

반응물 5

HCID 8471TriethylamineHCID 81531DiisopropylethylamineHCID 821294-Nitrophenyl chloroformateHCID 10921572(S)-2-Dimethylamino-1-phenylethanolHCID 67008245ethyl 3-amino-6,6-dimethyl-5,6-dihydropyrrolo[3,4-c]pyrazole-1(4H)-carboxylate dihydrochloride

생성물 1

HCID 67008599ethyl 3-amino-5({[(1S)-2-(dimethylamino)-1-phenylethyl]hydroxy}carbonyl)-6,6-dimethyl-5,6-dihydropyrrolo[3,4-c]pyrazole-1(4H)-carboxylate수율 20%

시약·촉매·용매 2

HCID 111,2-Dichloroethane용매HCID 6344Dichloromethane용매

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온도
50 °C

실험 절차

To a stirred solution of (S)-2-dimethylamino-1-phenyl-ethanol (68b, 21.50 g, 130.0 mmol) in 1,2-dichloroethane (500 mL) was added triethylamine (26.30 g, 260.0 mmol) and 4-nitrophenyl chloroformate (68c, 27.00 g, 130.0 mmol) at room temperature under nitrogen. The solution was stirred at 50° C. overnight. A total of 16.8 g (130.0 mmol) of Hünig's base was then added, followed by ethyl 3-amino-6,6-dimethyl-5,6-dihydropyrrolo[3,4-c]pyrazole-1(4H)-carboxylate dihydrochloride salt (54a, 17.90 g, 60.25 mmol). The reaction mixture was stirred at 50° C. for another 12 h. It was diluted with dichloromethane (1.5 L) and washed with water (2×1.0 L) and brine (1.0 L), dried over Na2SO4. Another batch with the exact scale was also carried out. These two batches were combined together during workup. Filtration and evaporation followed by flash chromatography (4.75% MeOH/0.25% NEt3/95% DCM) afforded compound 68e ethyl 3-amino-5({[(1S)-2-(dimethylamino)-1-phenylethyl]hydroxy}carbonyl)-6,6-dimethyl-5,6-dihydropyrrolo[3,4-c]pyrazole-1(4H)-carboxylate as a light-yellow gummy oil (5.00 g, 10%). 1H NMR (CDCl3, a mixture of rotamers, only the chemical shifts of the major form is reported) δ: 1.45 (t, J=7.1 Hz, 3H), 1.63 (s, 3H), 1.72 (s, 3H), 2.29 (s, 3H), 2.36 (s, 3H), 2.55-2.63 (m, 1H), 2.88 (dd, J=13, 8.3 Hz, 1H), 4.29 (q, J=13 Hz, 1H), 4.51 (q, J=7.1 Hz, 2H), 5.44 (d, J=10.7 Hz, 1H), 5.8-5.95 (m, 1H), 7.25-7.42 (m, 5H). LCMS (APCI, M+H+) 416.

후처리

  1. stirringThe reaction mixture was stirred at 50° C. for another 12 h
  2. washwashed with water (2×1.0 L) and brine (1.0 L)
  3. dry with materialdried over Na2SO4
  4. filtrationFiltration and evaporation

출처 및 근거

ORD 기록
ord-b552941dc0e44361ae1ad57b32657290
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08530652B2

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