Hydrochloric Acid → HCID 57415386, compound

HRID 1429087Notes

Reaction equation

HRID 1429087 reaction equation
[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]1[C:11]([O:20][C@H:21]2[CH2:54][N:24]3[C:25](=[O:53])[C@@H:26]([NH:45][C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][C:32]([F:44])([F:43])[CH2:33][C@@H:34]4[CH2:39][C@@:35]4([C:40](O)=[O:41])[NH:36][C:37](=[O:38])[C@@H:23]3[CH2:22]2)=[N:12][C:13]2[C:18]([N:19]=1)=[CH:17][CH:16]=[CH:15][CH:14]=2.C1N=CN(C(N2C=NC=C2)=O)C=1.[CH:67]1([S:70]([NH2:73])(=[O:72])=[O:71])[CH2:69][CH2:68]1.C1CCN2C(=NCCC2)CC1.Cl>ClCCl.ClCCCl>[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]1[C:11]([O:20][C@H:21]2[CH2:54][N:24]3[C:25](=[O:53])[C@@H:26]([NH:45][C:46](=[O:47])[O:48][C:49]([CH3:51])([CH3:52])[CH3:50])[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][C:32]([F:44])([F:43])[CH2:33][C@@H:34]4[CH2:39][C@@:35]4([C:40](=[O:41])[NH:73][S:70]([CH:67]4[CH2:69][CH2:68]4)(=[O:72])=[O:71])[NH:36][C:37](=[O:38])[C@@H:23]3[CH2:22]2)=[N:12][C:13]2[C:18]([N:19]=1)=[CH:17][CH:16]=[CH:15][CH:14]=2

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 682631,1'-CarbonyldiimidazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 15765418CyclopropanesulfonamideHCID 68008690HCID 68008690, compound

Product 1

HCID 57415386HCID 57415386, compoundYield 74%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of (2R,6S,13aS,14aR,16aS)-2-(3-(benzo[d]thiazol-2-yl)quinoxalin-2-yloxy)-6-(tert-butoxycarbonylamino)-12,12-difluoro-5,16-dioxooctadecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecine-14a-carboxylic acid (Example 13d, 6.22 mg, 8.13 μmol) was added molecular sieves and DCE (81 μl). CDI (2.91 mg, 0.018 mmol) was added, and the mixture was stirred at 40° C. for 2 h. The reaction mixture was cooled to rt and cyclopropanesulfonamide (2.4 mg, 0.020 mmol) was added followed by DBU (3 μl, 0.020 mmol). The mixture was stirred at rt for 2.5 h, diluted with dichloromethane and cooled to 0° C. The mixture was neutralized with HCl (14 μl, 4 N in dioxane, diluted with EA) and stirred for 5 min at 0° C., and evaporated under reduced pressure. The residue was purified by silica gel prep-TLC (dichloromethane/EA =1/1) to provide the title compound as a yellow solid, (5.2 mg, 74% yield). MS (ESI): m/z=868.3 [M+H], 866.3 [M−H].

Workup

  1. temperatureThe reaction mixture was cooled to rt
  2. stirringThe mixture was stirred at rt for 2.5 h
  3. temperaturecooled to 0° C
  4. stirringstirred for 5 min at 0° C.
  5. customevaporated under reduced pressure
  6. customThe residue was purified by silica gel prep-TLC (dichloromethane/EA =1/1)

Sources & evidence

ORD record
ord-22cb291cb9184f8aafe6ce1533f18168
Source dataset
uspto-grants-2015_01
Patent number
US08937041B2

Reaction notes

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