Trifluoroacetic acid → HCID 69458136, compound

HRID 1351949Notes

Reaction equation

HRID 1351949 reaction equation
[CH2:1]([N:3]([CH2:43][CH3:44])[C:4]([C:6]1[CH:7]=[CH:8][CH:9]=[C:10]2[C:14]=1[NH:13][CH:12]=[C:11]2[CH2:15][C@H:16]([N:18]([CH2:26][C@H:27]([OH:42])[C:28]1[CH:29]=[CH:30][C:31]2[O:36][CH2:35][CH2:34][N:33]([S:37]([CH3:40])(=[O:39])=[O:38])[C:32]=2[CH:41]=1)C(=O)OC(C)(C)C)[CH3:17])=[O:5])[CH3:2].[F:45][C:46]([F:51])([F:50])[C:47]([OH:49])=[O:48].C1(SC)C=CC=CC=1.C(=O)([O-])O.[Na+]>C(Cl)Cl>[F:45][C:46]([F:51])([F:50])[C:47]([OH:49])=[O:48].[CH2:43]([N:3]([CH2:1][CH3:2])[C:4]([C:6]1[CH:7]=[CH:8][CH:9]=[C:10]2[C:14]=1[NH:13][CH:12]=[C:11]2[CH2:15][C@H:16]([NH:18][CH2:26][C@H:27]([OH:42])[C:28]1[CH:29]=[CH:30][C:31]2[O:36][CH2:35][CH2:34][N:33]([S:37]([CH3:40])(=[O:39])=[O:38])[C:32]=2[CH:41]=1)[CH3:17])=[O:5])[CH3:44]

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acid3×HCID 7520ThioanisoleHCID 516892Sodium BicarbonateHCID 86760490HCID 86760490, compound

Product 1

HCID 69458136HCID 69458136, compoundYield 13%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl [2-(7-diethylcarbamoyl-1H-indol-3-yl)-(1R)-1-methylethyl]-[(2R)-2-hydroxy-2-(4-methanesulfonyl-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)ethyl]carbamate (48.4 mg, 0.077 mmol) in methylene chloride (3 mL) is added trifluoroacetic acid (250 μL) under nitrogen atmosphere, and the mixture is stirred at room temperature for 18 hours, and to the mixture is added trifluoroacetic acid (1 mL). The mixture is stirred at room temperature for 3 hours, and thereto are added trifluoroacetic acid (1 mL) and thioanisole (50 μL). The mixture is stirred at room temperature for one hour. The pH value of the reaction solution is adjusted to pH 8 with a saturated aqueous sodium hydrogen carbonate solution, and the solvent is distilled off. The residue is dissolved in chloroform:methanol (2:1, 75 mL), and the insoluble materials are removed by filtration. The solvent is removed by distillation, and the crude product is purified by preparative TLC (a saturated ammonia solution in chloroform) and prepartive HPLC (trifluoroacetic acid-acetonitrile-water) to give the desired 3-{(2R)-2-[(2R)-2-hydroxy-2-(4-methanesulfonyl-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)ethylamino]propyl}-1H-indole-7-carboxylic acid diethylamide trifluoroacetate (6.6 mg, 0.0103 mmol, yield: 13%).

Workup

  1. stirringThe mixture is stirred at room temperature for 3 hours
  2. stirringThe mixture is stirred at room temperature for one hour
  3. distillationthe solvent is distilled off
  4. dissolutionThe residue is dissolved in chloroform:methanol (2:1, 75 mL)
  5. customthe insoluble materials are removed by filtration
  6. customThe solvent is removed by distillation
  7. customthe crude product is purified by preparative TLC (a saturated ammonia solution in chloroform) and prepartive HPLC (trifluoroacetic acid-acetonitrile-water)

Sources & evidence

ORD record
ord-b044f61d3e6c400d9aa2d1503dcf69a6
Source dataset
uspto-grants-2007_05
Patent number
US07217724B2

Reaction notes

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