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 1674560Notes

Reaction equation

HRID 1674560 reaction equation
[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]

Participants

6

Reactant 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

Product 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 esterYield 51.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

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 hours, it was cooled to room temperature and treated sequentially with cyclopropylsulfonamide (135 mg, 1.12 mmol) and DBU (170 mg, 1.12 mmol). The reaction mixture was stirred for 4 hours at room temperature, 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), filtered, 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 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); LC-MS (Method A, retention time: 3.81 min), MS m/z 683 (M++1).

Workup

  1. customdried glassware
  2. temperaturemaintaining a dry N2 atmosphere)
  3. temperatureAfter refluxing the reaction mixture for 2 hours
  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. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto give the crude product
  10. customIt was then purified by flash chromatography (eluting with 33% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-676071035e704bd5b7512de6f2e5ce21
Source dataset
uspto-grants-2011_08
Patent number
US08003604B2

Reaction notes

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