1,1'-Carbonyldiimidazole → HCID 25014510, compound

HRID 1672149Notes

Reaction equation

HRID 1672149 reaction equation
[O:1]1[C:11]2=[C:12]3[C:7](=[CH:8][CH:9]=[C:10]2[C:13]([OH:15])=O)[CH:6]=[CH:5][N:4]3[CH:3]=[CH:2]1.C(N1[CH:27]=[CH:26]N=C1)(N1C=CN=C1)=O.[CH3:28][N:29]([CH3:34])[S:30]([NH2:33])(=[O:32])=[O:31].[CH2:35]1[CH2:45][CH2:44]N2[C:38](=NCCC2)[CH2:37][CH2:36]1>C1COCC1>[CH:35]1([C:6]2[C:7]3[C:12]4=[C:11]([O:1][CH2:2][CH2:3][N:4]4[C:5]=2[C:27]2[CH:26]=[CH:8][CH:7]=[CH:6][CH:5]=2)[C:10]([C:13]([NH:33][S:30]([N:29]([CH3:34])[CH3:28])(=[O:32])=[O:31])=[O:15])=[CH:9][CH:8]=3)[CH2:36][CH2:37][CH2:38][CH2:44][CH2:45]1

Participants

6

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 134472N,N-DimethylsulfamideHCID 67348557HCID 67348557, compound

Product 1

HCID 25014510HCID 25014510, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
50 °C

Procedure

To the acid (1,4-oxazino[2,3,4-hi]indole-9-carboxylic acid, 6-cyclohexyl-2,3-dihydro-5-phenyl-) (11.4 mg, 31.5 μmol) in a round-bottomed flask at r.t. under N2 was added a solution of 1,1′-carbonyldiimidazole (CDI) (10.2 mg, 62.9 μmol) in THF (1 ml), and the mixture was stirred at 50° C. for 2 hr. After cooling to r.t., the reaction mixture was added a mixture of N,N-dimethylsulfamide (15.6 mg, 126 μmol) and DBU (21.6 mg, 142 μmol) in THF (0.5 ml), and then stirred at 50° C. for 20.5 hr. After cooling to r.t., the volatiles were evaporated and the residue added hydrochloric acid (1.5 ml, 1N). The aqueous mixture was removed by pipet, and the solid residue purified by preparative thin layer chromatography (250 μm×20 cm×20 cm plate) using 5% MeOH/CH2Cl2 as eluent to give the product, which was then further purified by preparative thin layer chromatography (250 μm×20 cm×20 cm plate) using 20% EtOAc/Hexane as eluent to give the sulfamide (1,4-oxazino[2,3,4-hi]indole-9-carboxamide, 6-cyclohexyl-N-[(dimethylamino)sulfonyl]-2,3-dihydro-5-phenyl-). 1H NMR (500 MHz): (CDCl3—CD3OD) δ 7.60-7.44 (d overlapping with m, 7H), 4.76 (t, J=4.8, 2H), 4.19 (t, J=4.8, 2H), 3.03 (s, 6H), 2.80-2.70 (m, 1H), 2.05-1.88 (b m, 2H), 1.88-1.70 (b m, 4H), 1.45-1.25 (b m, 4H); Analytical HPLC method: Solvent A=10% MeOH-90% H2O-0.1% TFA, Solvent B=90% MeOH-10% H2O-0.1% TFA, Start % B=0, Final % B=100, Gradient time=2 min, Flow Rate=5 ml/min, Column: Xterra MS C18 S7 3.0×50 mm; LC/MS: (ES+) m/z (M+H)+=468.14, HPLC Rt=1.987 min.

Workup

  1. temperatureAfter cooling to r.t.
  2. additionthe reaction mixture was added
  3. stirringstirred at 50° C. for 20.5 hr
  4. temperatureAfter cooling to r.t.
  5. customthe volatiles were evaporated
  6. additionthe residue added hydrochloric acid (1.5 ml, 1N)
  7. customThe aqueous mixture was removed by pipet
  8. customthe solid residue purified by preparative thin layer chromatography (250 μm×20 cm×20 cm plate)
  9. customto give the product, which
  10. customwas then further purified by preparative thin layer chromatography (250 μm×20 cm×20 cm plate)

Sources & evidence

ORD record
ord-19345a81a2de48e394e39326ebdd5516
Source dataset
uspto-grants-2011_08
Patent number
US07998951B2

Reaction notes

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