tert-butyl ((2S,3S)-3-((R)-hex-5-en-2-yloxy)-1-((2S,4R)-4-hydroxy-2-(((1R,2S)-1-(((1-methylcyclopropyl)sulfonyl)carbamoyl)-2-vinylcyclopropyl)carbamoyl)pyrrolidin-1-yl)-1-oxopentan-2-yl)carbamate → tert-butyl ((2R,6S,7S,9R,13aS,14aR,16aS,Z)-7-ethyl-2-hydroxy-9-methyl-14a-(((1-methylcyclopropyl)sulfonyl)carbamoyl)-5,16-dioxo-2,3,5,6,7,9,10,11,13a,14,14a,15,16,16a-tetradecahydro-1H-cyclopropa[i]pyrrolo[1,2-e][1,5,8]oxadiazacyclopentadecin-6-yl)carbamate

HRID 523182

반응식

HRID 523182 반응식
[CH3:1][C@@H:2]([O:7][C@@H:8]([CH2:44][CH3:45])[C@H:9]([NH:36][C:37](=[O:43])[O:38][C:39]([CH3:42])([CH3:41])[CH3:40])[C:10]([N:12]1[CH2:16][C@H:15]([OH:17])[CH2:14][C@H:13]1[C:18](=[O:35])[NH:19][C@:20]1([C:25](=[O:34])[NH:26][S:27]([C:30]2([CH3:33])[CH2:32][CH2:31]2)(=[O:29])=[O:28])[CH2:22][C@H:21]1C=C)=[O:11])[CH2:3][CH2:4][CH:5]=[CH2:6]>CC1C=C(C)C=C(C)C=1N1CCN(C2C(C)=CC(C)=CC=2C)C1=[Ru](Cl)(Cl)=CC1C=CC=CC=1OC(C)C.ClCCCl>[CH2:44]([C@H:8]1[C@H:9]([NH:36][C:37](=[O:43])[O:38][C:39]([CH3:40])([CH3:42])[CH3:41])[C:10](=[O:11])[N:12]2[CH2:16][C@H:15]([OH:17])[CH2:14][C@H:13]2[C:18](=[O:35])[NH:19][C@:20]2([C:25](=[O:34])[NH:26][S:27]([C:30]3([CH3:33])[CH2:31][CH2:32]3)(=[O:29])=[O:28])[CH2:21][C@H:22]2[CH:6]=[CH:5][CH2:4][CH2:3][C@@H:2]([CH3:1])[O:7]1)[CH3:45]

참가 물질

4

반응물 1

HCID 118425558tert-butyl ((2S,3S)-3-((R)-hex-5-en-2-yloxy)-1-((2S,4R)-4-hydroxy-2-(((1R,2S)-1-(((1-methylcyclopropyl)sulfonyl)carbamoyl)-2-vinylcyclopropyl)carbamoyl)pyrrolidin-1-yl)-1-oxopentan-2-yl)carbamate

생성물 1

HCID 90132196tert-butyl ((2R,6S,7S,9R,13aS,14aR,16aS,Z)-7-ethyl-2-hydroxy-9-methyl-14a-(((1-methylcyclopropyl)sulfonyl)carbamoyl)-5,16-dioxo-2,3,5,6,7,9,10,11,13a,14,14a,15,16,16a-tetradecahydro-1H-cyclopropa[i]pyrrolo[1,2-e][1,5,8]oxadiazacyclopentadecin-6-yl)carbamate

시약·촉매·용매 2

HCID 11763533(1,3-Bis(2,4,6-trimethylphenyl)imidazolidin-2-ylidene)(dichloro)((2-((propan-2-yl)oxy)phenyl)methylidene)ruthenium촉매HCID 111,2-Dichloroethane용매

반응 조건

온도
80 °C

실험 절차

To a round-bottom flask equipped with a stir bar was added tert-butyl ((2S,3S)-3-((R)-hex-5-en-2-yloxy)-1-((2S,4R)-4-hydroxy-2-(((1R,2S)-1-(((1-methylcyclopropyl)sulfonyl)carbamoyl)-2-vinylcyclopropyl)carbamoyl)pyrrolidin-1-yl)-1-oxopentan-2-yl)carbamate (all material from step 4, 569 mg, 0.869 mmol) and DCE (100 mL). The solution was sparged with nitrogen for 30 min. and then to the solution was added (1,3-Bis-(2,4,6-trimethylphenyl)-2-imidazolidinylidene)dichloro(o-isopropoxyphenylmethylene)ruthenium (“Hoveyda-Grubbs Catalyst 2nd Generation”, 27 mg, 0.043 mmol). The solution was stirred at 80° C. for 2 h and then cooled to 45° C. and stirred for 3 days. The solution was concentrated in vacuo and the resulting residue was subjected to silica gel purification (hexanes:acetone 80:20 to 40:60). The product containing fractions were pooled; concentrated; and re-subjected to silica gel chromatography (hexanes:acetone 80:20 to 40:60) to afford tert-butyl ((2R,6S,7S,9R,13aS,14aR,16aS,Z)-7-ethyl-2-hydroxy-9-methyl-14a-(((1-methylcyclopropyl)sulfonyl)carbamoyl)-5,16-dioxo-2,3,5,6,7,9,10,11,13a,14,14a,15,16,16a-tetradecahydro-1H-cyclopropa[i]pyrrolo[1,2-e][1,5,8]oxadiazacyclopentadecin-6-yl)carbamate as a light-brown solid foam (90 mg, 10% over 5 steps). 1H-NMR (500 MHz, CD3OD) δ 8.93 (s, 1H), 5.61 (td, J=10.1, 6.2 Hz, 1H), 5.03 (t, J=10.3 Hz, 1H), 4.58 (br. s., 1H), 4.47-4.37 (m, 2H), 3.92 (br. s., 2H), 3.86-3.79 (m, 1H), 3.58-3.49 (m, 1H), 2.75 (q, J=9.5 Hz, 1H), 2.64-2.52 (m, 1H), 2.23-2.11 (m, 2H), 1.92-1.80 (m, 2H), 1.75 (dd, J=8.5, 5.5 Hz, 1H), 1.66-1.60 (m, 1H), 1.59-1.52 (m, 2H), 1.49 (s, 4H), 1.43 (s, 9H), 1.41-1.32 (m, 2H), 1.15 (d, J=6.3 Hz, 3H), 0.95 (t, J=7.4 Hz, 3H), 0.88-0.84 (m, 2H).

후처리

  1. customTo a round-bottom flask equipped with a stir bar
  2. customThe solution was sparged with nitrogen for 30 min.
  3. temperaturecooled to 45° C.
  4. stirringstirred for 3 days
  5. concentrationThe solution was concentrated in vacuo
  6. customthe resulting residue was subjected to silica gel purification (hexanes:acetone 80:20 to 40:60)
  7. additionThe product containing fractions
  8. concentrationconcentrated

출처 및 근거

ORD 기록
ord-0f40bc58e2ce4249815c092e2b578bda
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09334279B2

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