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 563900ノート

反応式

HRID 563900 の反応式
[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

参加物

8

反応物 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

生成物 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)-carboxylate収率 20%

試薬・触媒・溶媒 2

HCID 111,2-Dichloroethane溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
50 °C

実験手順

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, 2H0, 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.

後処理

  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

出典と根拠

ORDレコード
ord-8ea8c9f6243d48afb003dc2d2cb3becb
出典データセット
uspto-grants-2011_11
特許番号
US08067591B2

反応ノート

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