Carbamate → (3-Cyano-5-methoxy-phenyl)-carbamic acid 4-cyclopropanesulfonylaminocarbonyl-13-methyl-2,14-dioxo-3,13-diaza-tricyclo[13.3.0.0*4,6*]octadec-7-en-17-yl ester

HRID 390119Notes

Reaction equation

HRID 390119 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.[NH2:41][C:42]1[CH:43]=[C:44]([CH:47]=[C:48]([O:50][CH3:51])[CH:49]=1)[C:45]#[N:46].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](=[O:35])[NH:41][C:42]4[CH:49]=[C:48]([O:50][CH3:51])[CH:47]=[C:44]([C:45]#[N:46])[CH:43]=4)[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 516892Sodium BicarbonateHCID 107731223-Amino-5-methoxybenzonitrileHCID 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 68707550(3-Cyano-5-methoxy-phenyl)-carbamic acid 4-cyclopropanesulfonylaminocarbonyl-13-methyl-2,14-dioxo-3,13-diaza-tricyclo[13.3.0.0*4,6*]octadec-7-en-17-yl esterYield 8%

Reagents, catalysts & solvents 4

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

Conditions

Temperature
100 °C

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 (full conversion to chloroimidate according to LC-MS) 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), 3-amino-5-methoxy-benzonitrile (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 aniline, followed by dichloromethane and then 2% methanol in dichloromethane) to give the title compound as a powder (15 mg, 8%), [M+H]+ 628.

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. concentrationconcentrated by rotary evaporation
  5. custompurified by column chromatography on YMC silica (15 g, ethyl acetate/petroleum ether 1:3
  6. customto remove excess of aniline

Sources & evidence

ORD record
ord-e67d8b929c5944748804c4dfdaee9da3
Source dataset
uspto-grants-2013_02
Patent number
US08383584B2

Reaction notes

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