Dimethylformamide → HCID 68008851, compound

HRID 1429083Notes

Reaction equation

HRID 1429083 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]([OH:28])[CH2:27][C@H:21]2[C:20](=[O:29])[NH:19][C@:18]2([C:31]([OH:33])=[O:32])[CH2:30][C@H:17]2[CH2:16][C:15]([F:35])([F:34])[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl[C:37]1[C:46]([CH2:47][CH3:48])=[N:45][C:44]2[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=2)[N:38]=1.CN(C=O)C.CCC([O-])(C)C.[Na+]>CC#N.Cl>[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:37]3[C:46]([CH2:47][CH3:48])=[N:45][C:44]4[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=4)[N:38]=3)[CH2:27][C@H:21]2[C:20](=[O:29])[NH:19][C@:18]2([C:31]([OH:33])=[O:32])[CH2:30][C@H:17]2[CH2:16][C:15]([F:35])([F:34])[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 2733478Sodium 2-methylbutan-2-olate2×HCID 27795362-chloro-3-ethylquinoxaline2×HCID 68008615HCID 68008615, compound

Product 1

HCID 68008851HCID 68008851, compoundYield 57.5%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 6342AcetonitrileSolvent

Procedure

To (2R,6S,13aS,14aR,16aS)-6-(tert-butoxycarbonylamino)-12,12-difluoro-2-hydroxy-5,16-dioxooctadecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecine-14a-carboxylic acid (Example 7j, 87.4 mg, 0.174 mmol) was added 2-chloro-3-ethylquinoxaline (47.7 mg, 0.247 mmol) and DMF (868 μl). To this solution was added sodium tert-pentoxide (48.9 mg, 0.444 mmol) at room temperature, and the mixture turned dark purple (slightly exothermic). The reaction mixture was stirred at room temperature for 17 h. Additional 2-chloro-3-ethylquinoxaline (18.1 mg, 0.094 mmol) and sodium tert-pentoxide (24.2 mg, 0.202 mmol) were added, and the reaction mixture was stirred for 22 h. The reaction mixture was diluted with CH3CN and neutralized with HCl (1 N, 0.7 ml) and evaporated under reduced pressure. The residue was purified by reverse phase HPLC (CH3CN/H2O (0.1%TFA), gradient=20/80-85/15) to provide the title compound as a light brown solid, (2R,6S,13aS,14aR,16aS)-6-(tert-butoxycarbonylamino)-2-(3-ethylquinoxalin-2-yloxy)-12,12-difluoro-5,16-dioxooctadecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecine-14a-carboxylic acid (66 mg, 57% yield).

Workup

  1. stirringthe reaction mixture was stirred for 22 h
  2. customevaporated under reduced pressure
  3. customThe residue was purified by reverse phase HPLC (CH3CN/H2O (0.1%TFA), gradient=20/80-85/15)

Sources & evidence

ORD record
ord-2145715a38d24e559088cc15146b3087
Source dataset
uspto-grants-2015_01
Patent number
US08937041B2

Reaction notes

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