1,1'-Carbonyldiimidazole → HCID 86683205, compound

HRID 1852130Notes

Reaction equation

HRID 1852130 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]1[C:23](=[O:24])[N:22]2[CH2:25][C@H:26]([O:28][C:29]3[C:38]4[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=4)[C:32]([O:39][CH3:40])=[CH:31][N:30]=3)[CH2:27][C@H:21]2[C:20](=[O:41])[NH:19][C@:18]2([C:43]([OH:45])=O)[CH2:42][C@H:17]2[CH:16]=[CH:15][CH2:14][CH2:13][CH:12]([CH3:46])[CH2:11][C@H:10]1[CH3:47])=[O:7])([CH3:4])([CH3:3])[CH3:2].C1N=CN(C(N2C=NC=C2)=O)C=1.[CH:60]1([S:64]([NH2:67])(=[O:66])=[O:65])[CH2:63][CH2:62][CH2:61]1.C1CCN2C(=NCCC2)CC1>O1CCCC1>[CH:60]1([S:64]([NH:67][C:43]([C@@:18]23[CH2:42][C@H:17]2[CH:16]=[CH:15][CH2:14][CH2:13][CH:12]([CH3:46])[CH2:11][C@@H:10]([CH3:47])[C@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:4])([CH3:3])[CH3:2])[C:23](=[O:24])[N:22]2[CH2:25][C@H:26]([O:28][C:29]4[C:38]5[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=5)[C:32]([O:39][CH3:40])=[CH:31][N:30]=4)[CH2:27][C@H:21]2[C:20](=[O:41])[NH:19]3)=[O:45])(=[O:66])=[O:65])[CH2:63][CH2:62][CH2:61]1

Participants

6

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 15238957CyclobutanesulfonamideHCID 86683204HCID 86683204, compound

Product 1

HCID 86683205HCID 86683205, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of (2R,6S,7R,13aS,14aR,16aS,Z)-6-((tert-butoxycarbonyl)amino)-2-((4-methoxyisoquinolin-1-yl)oxy)-7,9-dimethyl-5,16-dioxo-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 (70 mg, 0.108 mmol), CDI (34.9 mg, 0.215 mmol) in tetrahydrofuran (3 mL) was refluxed for 2 h. It was then cooled to rt and cyclobutanesulfonamide (32.0 mg, 0.237 mmol) was added and followed by DBU (0.036 mL, 0.237 mmol). The mixture was stirred at rt for 16 h. It was then concentrated and purified by silica gel chromatography, eluting with 40% acetone/hexane to isolate 70 mg of the diastereomers tert-butyl ((2R,6S,7R,13aS,14aR,16aS,Z)-14a-((cyclobutylsulfonyl)carbamoyl)-2-((4-methoxyisoquinolin-1-yl)oxy)-7,9-dimethyl-5,16-dioxo-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-yl)carbamate that was used as it was.

Workup

  1. temperaturewas refluxed for 2 h
  2. concentrationIt was then concentrated
  3. custompurified by silica gel chromatography
  4. washeluting with 40% acetone/hexane

Sources & evidence

ORD record
ord-6bfea4cba64045bdb0bdf3e962465e0d
Source dataset
uspto-grants-2015_02
Patent number
US08957203B2

Reaction notes

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