1,1'-Carbonyldiimidazole → tert-butyl (R)-{2-[7-(2-methanesulfonylamino-2-oxo-ethoxy)-1H-indol-3-yl]-1-methylethyl}carbamate

HRID 1351929Notes

Reaction equation

HRID 1351929 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([CH3:25])[CH2:10][C:11]1[C:19]2[C:14](=[C:15]([O:20][CH2:21][C:22](O)=[O:23])[CH:16]=[CH:17][CH:18]=2)[NH:13][CH:12]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N1C=CN=C1)(N1C=CN=C1)=O.[CH3:38][S:39]([NH2:42])(=[O:41])=[O:40].N12CCCN=C1CCCCC2>CN(C)C=O.O>[CH3:38][S:39]([NH:42][C:22](=[O:23])[CH2:21][O:20][C:15]1[CH:16]=[CH:17][CH:18]=[C:19]2[C:14]=1[NH:13][CH:12]=[C:11]2[CH2:10][C@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:4])([CH3:3])[CH3:2])[CH3:25])(=[O:41])=[O:40]

Participants

7

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 72879MethanesulfonamideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 69459193(R)-[3-(2-(tert-butoxycarbonylamino)propyl)-1H-indol-7-yloxy]acetic acid

Product 1

HCID 86604018tert-butyl (R)-{2-[7-(2-methanesulfonylamino-2-oxo-ethoxy)-1H-indol-3-yl]-1-methylethyl}carbamateYield 38.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

A solution of (R)-[3-(2-(tert-butoxycarbonylamino)propyl)-1H-indol-7-yloxy]acetic acid (0.30 g, 0.86 mmol) and carbonyldiimidazole (0.21 g, 1.3 mmol) in dimethylformamide (10 mL) is stirred at room temperature for 3 days. To the mixture are added methanesulfonamide (0.16 g, 1.7 mmol) and 1,8-diazabicyclo[5.4.0]undeca-7-ene (0.26 mL, 1.7 mmol), and the mixture is stirred at 50° C. for 4 hours. After cooling, to the mixture is added water (0.1 mL), and the mixture is concentrated. The residue is purified by silica gel column chromatography (methanol/chloroform=1/10→1/3), and the resultant is dissolved in ethyl acetate, washed with a 0.05N hydrochloric acid (×2) and saturated brine, and further dried over magnesium sulfate and concentrated to give the desired tert-butyl (R)-{2-[7-(2-methanesulfonylamino-2-oxo-ethoxy)-1H-indol-3-yl]-1-methylethyl}carbamate (0.14 g, yield: 38%).

Workup

  1. temperatureAfter cooling, to the mixture
  2. concentrationthe mixture is concentrated
  3. customThe residue is purified by silica gel column chromatography (methanol/chloroform=1/10→1/3)
  4. dissolutionthe resultant is dissolved in ethyl acetate
  5. washwashed with a 0.05N hydrochloric acid (×2) and saturated brine
  6. dry with materialfurther dried over magnesium sulfate
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-d0b5aee107f94748962d6e3fb5b410bb
Source dataset
uspto-grants-2007_05
Patent number
US07217724B2

Reaction notes

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