Carbamate → 6H-Phenanthridine-5-carboxylic acid 4-cyclopropanesulfonylaminocarbonyl-13-methyl-2,14-dioxo-3,13-diaza-tricyclo[13.3.0.04,6]octadec-7-en-17-yl ester

HRID 390134Notes

Reaction equation

HRID 390134 reaction equation
[OH:1][CH:2]1[CH2:19][CH:18]2[CH:4]([C:5](=[O:31])[N:6]([CH3:30])[CH2:7][CH2:8][CH2:9][CH2:10][CH:11]=[CH:12][CH:13]3[C:15]([C:21]([NH:23][S:24]([CH:27]4[CH2:29][CH2:28]4)(=[O:26])=[O:25])=[O:22])([NH:16][C:17]2=[O:20])[CH2:14]3)[CH2:3]1.[C:32](=[O:35])(O)[O-].[Na+].C(Cl)(Cl)=O.[CH:41]1[C:54]2[C:53]3[C:48](=[CH:49][CH:50]=[CH:51][CH:52]=3)[CH2:47][NH:46][C:45]=2[CH:44]=[CH:43][CH:42]=1.C(=O)([O-])[O-].[K+].[K+].C(=O)([O-])N>ClCCCl.C1(C)C=CC=CC=1.C(Cl)Cl.CO>[CH:27]1([S:24]([NH:23][C:21]([C:15]23[CH2:14][CH:13]2[CH:12]=[CH:11][CH2:10][CH2:9][CH2:8][CH2:7][N:6]([CH3:30])[C:5](=[O:31])[CH:4]2[CH:18]([CH2:19][CH:2]([O:1][C:32]([N:46]4[CH2:47][C:48]5[C:53](=[CH:52][CH:51]=[CH:50][CH:49]=5)[C:54]5[CH:41]=[CH:42][CH:43]=[CH:44][C:45]4=5)=[O:35])[CH2:3]2)[C:17](=[O:20])[NH:16]3)=[O:22])(=[O:26])=[O:25])[CH2:28][CH2:29]1

Participants

11

Reactant 6

HCID 276CarbamateHCID 6371PhosgeneHCID 11430Potassium CarbonateHCID 2199665,6-DihydrophenanthridineHCID 516892Sodium BicarbonateHCID 72539645Cyclopropanesulphonic acid (17-hydroxy-13-methyl-2,14-dioxo-3,13-diazatricyclo[13.3.0.0*4,6*]octadec-7-ene-4-carbonyl)-amide

Product 1

HCID 725396446H-Phenanthridine-5-carboxylic acid 4-cyclopropanesulfonylaminocarbonyl-13-methyl-2,14-dioxo-3,13-diaza-tricyclo[13.3.0.04,6]octadec-7-en-17-yl ester

Reagents, catalysts & solvents 4

HCID 111,2-DichloroethaneSolvent2×HCID 887MethanolSolventHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent2×

Procedure

The alcohol 1h (15 mg) was dissolved in dry DCE and 20 mg of sodium bicarbonate was added, followed by 2 ml of a phosgene solution in toluene (20%). The reaction mixture was stirred at room temperature for 3 h and then concentrated by rotary evaporation and dried from excess of phosgene in high vacuum (1.5 h). The dry reaction mixture was transferred into a “microwave” vial (2-5 ml), mixed with dry DCE (3 ml), 5,6-dihydro-phenanthridine (1k) (2 eq), potassium carbonate (9 mg, 1.5 eq), pulverized molecular sieves (4 Å, 5 mg) and heated in a microwave at 100° C. for 45 min. The reaction mixture was passed through short pad of silica (eluent DCM, then 10% methanol in DCM). The resulting fractions containing the desired carbamate compound were combined, concentrated by rotary evaporation and purified by column chromatography on YMC silica (15 g, ethyl acetate/petroleum ether 1:3 to remove excess of 5,6-dihydro-phenanthridine (1k), followed by dichloromethane and then 2% methanol in dichloromethane) to give the title compound as a powder.

Workup

  1. concentrationconcentrated by rotary evaporation
  2. dry with materialdried from excess of phosgene in high vacuum (1.5 h)
  3. customThe dry reaction mixture
  4. temperatureheated in a microwave at 100° C. for 45 min
  5. concentrationconcentrated by rotary evaporation
  6. custompurified by column chromatography on YMC silica (15 g, ethyl acetate/petroleum ether 1:3
  7. customto remove excess of 5,6-dihydro-phenanthridine (1k)

Sources & evidence

ORD record
ord-7eacb9b1b321465eba75c16a8bf7f597
Source dataset
uspto-grants-2013_02
Patent number
US08383584B2

Reaction notes

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