Hydrochloric Acid → HCID 71008676, compound

HRID 1845972Notes

Reaction equation

HRID 1845972 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]2[C:14]([CH:15]=1)=[N:13][C:12]([O:16][C@H:17]1[CH2:49][N:20]3[C:21](=[O:48])[C@@H:22]([NH:39][C:40]([C:42]4[CH:46]=[C:45]([CH3:47])[O:44][N:43]=4)=[O:41])[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH:28]=[CH:29][C@@H:30]4[CH2:35][C@@:31]4([C:36](O)=[O:37])[NH:32][C:33](=[O:34])[C@@H:19]3[CH2:18]1)=[C:11]1[C:6]=2[CH:7]=[CH:8][CH:9]=[CH:10]1.C(N1C=CN=C1)(N1C=CN=C1)=O.[CH3:62][C:63]1([S:66]([NH2:69])(=[O:68])=[O:67])[CH2:65][CH2:64]1.Cl.O1CCOCC1>ClC(Cl)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]2[C:14]([CH:15]=1)=[N:13][C:12]([O:16][C@H:17]1[CH2:49][N:20]3[C:21](=[O:48])[C@@H:22]([NH:39][C:40]([C:42]4[CH:46]=[C:45]([CH3:47])[O:44][N:43]=4)=[O:41])[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH:28]=[CH:29][C@@H:30]4[CH2:35][C@@:31]4([C:36](=[O:37])[NH:69][S:66]([C:63]4([CH3:62])[CH2:65][CH2:64]4)(=[O:68])=[O:67])[NH:32][C:33](=[O:34])[C@@H:19]3[CH2:18]1)=[C:11]1[C:6]=2[CH:7]=[CH:8][CH:9]=[CH:10]1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 682631,1'-CarbonyldiimidazoleHCID 218898141-Methylcyclopropane-1-sulfonamideHCID 71008354HCID 71008354, compound2×

Product 1

HCID 71008676HCID 71008676, compoundYield 47%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Conditions

Temperature
40 °C

Procedure

The product of Example 1f, (2R,6S,13aS,14aR,16aS,Z)-2-(3-fluorophenanthridin-6-yloxy)-6-(5-methylisoxazole-3-carboxamido)-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 (0.812 g, 1.21 mmol) was dissolved in dichloroethane (12 mL) and 4A sieves were added to the flask. To this mixture was added carbonyldiimidazole (505 mg, 3.11 mmol) and the reaction mixture was heated at 40° C. for 2 h. The reaction mixture was cooled to room temperature and 1-methylcyclopropane-1-sulfonamide (426 mg, 3.15 mmol) was added followed by 1,8-diazabicycloundecene (0.548 ml, 3.64 mmol). The reaction mixture was stirred at room temperature for 3 h. and then cooled to 0° C. and 4 N HCl in dioxane (2.5 mL, 10 mmol) was added. The resulting solid was washed copiously with dichloromethane and the filtrate was washed with 2 N HCl and then water. The organic layer was dried over anhydrous magnesium sulfate, filtered, and evaporated under reduced pressure. The residue was purified by flash chromatography on silica gel eluting with acetone/hexane followed by acetone/chloroform to provide the title compound (0.45 g, 47% yield) as a white solid. MS (ESI): m/z=787.2 [M+H]+.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. temperaturecooled to 0° C.
  3. washThe resulting solid was washed copiously with dichloromethane
  4. washthe filtrate was washed with 2 N HCl
  5. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. customevaporated under reduced pressure
  8. customThe residue was purified by flash chromatography on silica gel eluting with acetone/hexane

Sources & evidence

ORD record
ord-39bd383f66bd4158a98664784d0f30cc
Source dataset
uspto-grants-2015_02
Patent number
US08951964B2

Reaction notes

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