1,1'-Carbonyldiimidazole → [18-(Tert-butyl-dimethyl-silanyloxy)-4-cyclopropanesulfonylaminocarbonyl-2,15-dioxo-3,16-diaza-tricyclo[14.3.0.04,6]nonadec-7-en-14-yl]-carbamic acid tert-butyl ester

HRID 1674536

反応式

HRID 1674536 の反応式
[C:1]([O:5][C:6]([NH:8][CH:9]1[C:27](=[O:28])[N:26]2[CH:22]([CH2:23][CH:24]([O:29][Si:30]([C:33]([CH3:36])([CH3:35])[CH3:34])([CH3:32])[CH3:31])[CH2:25]2)[C:21](=[O:37])[NH:20][C:19]2([C:38]([OH:40])=O)[CH:17]([CH2:18]2)[CH:16]=[CH:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1N=CN(C(N2C=NC=C2)=O)C=1.[CH:53]1([S:56]([NH2:59])(=[O:58])=[O:57])[CH2:55][CH2:54]1.C1CCN2C(=NCCC2)CC1>C1COCC1>[C:1]([O:5][C:6](=[O:7])[NH:8][CH:9]1[C:27](=[O:28])[N:26]2[CH:22]([CH2:23][CH:24]([O:29][Si:30]([C:33]([CH3:35])([CH3:36])[CH3:34])([CH3:31])[CH3:32])[CH2:25]2)[C:21](=[O:37])[NH:20][C:19]2([C:38]([NH:59][S:56]([CH:53]3[CH2:55][CH2:54]3)(=[O:58])=[O:57])=[O:40])[CH:17]([CH2:18]2)[CH:16]=[CH:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1)([CH3:3])([CH3:4])[CH3:2]

参加物

6

反応物 4

HCID 682631,1'-CarbonyldiimidazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 15765418CyclopropanesulfonamideHCID 6732983314-tert-Butoxycarbonylamino-18-(tert-butyldimethylsilanyloxy)-2,15-dioxo-3,16-diaza-tricyclo[14.3.0.04,6]nonadec-7-ene-4-carboxylic acid

生成物 1

HCID 66915233[18-(Tert-butyl-dimethyl-silanyloxy)-4-cyclopropanesulfonylaminocarbonyl-2,15-dioxo-3,16-diaza-tricyclo[14.3.0.04,6]nonadec-7-en-14-yl]-carbamic acid tert-butyl ester収率 51.1%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

14-tert-Butoxycarbonylamino-18-(tert-butyl-dimethyl-silanyloxy)-2,15-dioxo-3,16-diaza-tricyclo[14.3.0.04,6]nonadec-7-ene-4-carboxylic acid (500 mg, 0.86 mmol.) was dissolved in 25 mL of THF and treated with CDI (180 mg, 1.12 mmol.). (Care was taken to avoid moisture by using oven dried glassware and maintaining a dry N2 atmosphere). After refluxing the reaction mixture for 2 h, it was cooled to rt and treated sequentially with cyclopropylsulfonamide (135 mg, 1.12 mmol.) and DBU (170 mg, 1.12 mmol.). The reaction mixture was stirred for 4 h at rt, and the THF was removed by rotary evaporation. The residue was partitioned between ethyl acetate and pH 4 buffer. The organic phase was dried (MgSO4) and concentrated in vacuo to give the crude product. It was then purified by flash chromatography (eluting with 33% ethyl acetate in hexane) to give 300 mg (51%) of [18-(tert-butyl-dimethyl-silanyloxy)-4-cyclopropanesulfonylaminocarbonyl-2,15-dioxo-3,16-diaza-tricyclo[14.3.0.04,6]nonadec-7-en-14-yl]-carbamic acid tert-butyl ester as a white solid. 1H NMR (300 MHz, CD3OD) δ 1H 0.07 (s, 3H), 0.08 (s, 3H), 0.85 (s, 9H), 0.87-1.49 (m, 21H), 1.73-1.95 (m, 3H), 2.08-2.16 (m, 1H), 2.25-2.36 (m, 2H), 2.42-2.56 (m, 1H), 2.85-2.93 (m, 1H), 3.65-3.74 (dd, J=10.61, 3.66 Hz, 1H), 3.89 (d, J=10.25 Hz, 1H), 4.34 (m, J=9.70, 9.70 Hz, 1H), 4.43 (t, J=7.87 Hz, 1H), 4.57 (s, 1H), 4.94-5.01 (m, 1H), 5.10 (d, J=8.78 Hz, 1H), 5.66-5.75 (m, 1H), 6.55 (s, 1H), 10.13 (s, 1H); MS m/z 683 (M++1).

後処理

  1. customdried glassware
  2. temperaturemaintaining a dry N2 atmosphere)
  3. temperatureAfter refluxing the reaction mixture for 2 h
  4. customthe THF was removed by rotary evaporation
  5. customThe residue was partitioned between ethyl acetate and pH 4 buffer
  6. dry with materialThe organic phase was dried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. customto give the crude product
  9. customIt was then purified by flash chromatography (eluting with 33% ethyl acetate in hexane)

出典と根拠

ORDレコード
ord-8dc8548fcd7c4dda818a0764a67c7adf
出典データセット
uspto-grants-2011_08
特許番号
US08003604B2

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