1,1'-Carbonyldiimidazole → HCID 57988327, compound

HRID 1666538Notes

Reaction equation

HRID 1666538 reaction equation
[C:1]1([C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)[CH:6]=[CH:5][C:4]([C@@:7]2([S:39]([CH2:42][CH2:43][CH3:44])(=[O:41])=[O:40])[CH2:38][N:10]3[C:11](=[O:37])[C@@H:12]([NH:29][C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH:18]=[CH:19][C@@H:20]4[CH2:25][C@@:21]4([C:26](O)=[O:27])[NH:22][C:23](=[O:24])[C@@H:9]3[CH2:8]2)=[CH:3][CH:2]=1.C1N=CN(C(N2C=NC=C2)=O)C=1.[CH:63]1([S:66]([NH2:69])(=[O:68])=[O:67])[CH2:65][CH2:64]1.C1CCN2C(=NCCC2)CC1>O1CCCC1>[C:1]1([C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)[CH:2]=[CH:3][C:4]([C@@:7]2([S:39]([CH2:42][CH2:43][CH3:44])(=[O:41])=[O:40])[CH2:38][N:10]3[C:11](=[O:37])[C@@H:12]([NH:29][C:30](=[O:31])[O:32][C:33]([CH3:35])([CH3:36])[CH3:34])[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH:18]=[CH:19][C@@H:20]4[CH2:25][C@@:21]4([C:26](=[O:27])[NH:69][S:66]([CH:63]4[CH2:65][CH2:64]4)(=[O:68])=[O:67])[NH:22][C:23](=[O:24])[C@@H:9]3[CH2:8]2)=[CH:5][CH:6]=1

Participants

6

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 15765418CyclopropanesulfonamideHCID 57988331HCID 57988331, compound

Product 1

HCID 57988327HCID 57988327, compoundYield 71.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of (2R,6S,13aS,14aR,16aS,Z)-2-(biphenyl-4-yl)-6-(tert-butoxycarbonylamino)-5,16-dioxo-2-(propylsulfonyl)-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecine-14a-carboxylic acid (995 mg, 1.406 mmol) and CDI (274 mg, 1.687 mmol) in tetrahydrofuran (20 mL) was heated to gentle reflux for 3 h. Cooled down to rt, cyclopropanesulfonamide (204 mg, 1.687 mmol) and DBU (0.424 mL, 2.81 mmol) were added and the reaction continued at r.t. for 4 h. Removed the solvent in vacuo. The residue was taken up in EtOAc. Washed it with 5% citric acid and brine, dried over MgSO4, filtered, evaporated. The residue was purified by BIOTAGE® system, eluted with gradient 10%˜50% acetone-hexane to afford the desired product tert-butyl (2R,6S,13aS,14aR,16aS,Z)-2-(biphenyl-4-yl)-14a-(cyclopropylsulfonylcarbamoyl)-5,16-dioxo-2-(propylsulfonyl)-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecin-6-ylcarbamate (827 mg, 0.999 mmol, 71.1% yield) as a white solid. 1H NMR (400 MHz, MeOD) δ ppm 0.87-1.09 (m, 5 H) 1.06-1.22 (m, 2 H) 1.24-1.40 (m, 3 H) 1.39-1.66 (m, 17 H) 1.64-1.79 (m, 3 H) 1.82-2.03 (m, 2 H) 2.39 (d, J=8.53 Hz, 1 H) 2.65 (br. s., 1 H) 2.75-3.01 (m, 3 H) 3.05-3.27 (m, 2 H) 4.14 (dd, J=10.04, 6.53 Hz, 1 H) 4.43 (d, J=10.54 Hz, 2 H) 4.54 (s, 1 H) 5.11 (br. s., 1 H) 5.34 (d, J=10.54 Hz, 1 H) 5.70 (q, J=8.53 Hz, 1 H) 7.35-7.43 (m, 1 H) 7.48 (t, J=7.65 Hz, 2 H) 7.63 (d, J=7.53 Hz, 2 H) 7.72 (d, J=8.28 Hz, 2 H) 7.98 (d, J=8.28 Hz, 2 H). LC-MS (retention time: 1.92 min, method A), MS m/z 811 (M+H).

Workup

  1. temperatureto gentle reflux for 3 h
  2. customRemoved the solvent in vacuo
  3. washWashed it with 5% citric acid and brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by BIOTAGE® system
  8. washeluted with gradient 10%˜50% acetone-hexane

Sources & evidence

ORD record
ord-c5bf649e28164d379f935ae539ddabe8
Source dataset
uspto-grants-2011_10
Patent number
US08044023B2

Reaction notes

Loading…