Sodium hydride → {6-[1-(5-tert-Butyl-isoxazol-3-ylcarbamoyl)-4-fluoro-2-methyl-1H-indol-5-yloxy]-pyrimidin-4-ylmethyl}-methyl-carbamic acid tert-butyl ester

HRID 453203Notes

Reaction equation

HRID 453203 reaction equation
[C:1]([O:5][C:6](=[O:28])[N:7]([CH2:9][C:10]1[CH:15]=[C:14]([O:16][C:17]2[C:18]([F:27])=[C:19]3[C:23](=[CH:24][CH:25]=2)[NH:22][C:21]([CH3:26])=[CH:20]3)[N:13]=[CH:12][N:11]=1)[CH3:8])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].C1([O:37][C:38](=O)[NH:39][C:40]2[CH:44]=[C:43]([C:45]([CH3:48])([CH3:47])[CH3:46])[O:42][N:41]=2)C=CC=CC=1>C1COCC1>[C:1]([O:5][C:6](=[O:28])[N:7]([CH2:9][C:10]1[CH:15]=[C:14]([O:16][C:17]2[C:18]([F:27])=[C:19]3[C:23](=[CH:24][CH:25]=2)[N:22]([C:38](=[O:37])[NH:39][C:40]2[CH:44]=[C:43]([C:45]([CH3:47])([CH3:46])[CH3:48])[O:42][N:41]=2)[C:21]([CH3:26])=[CH:20]3)[N:13]=[CH:12][N:11]=1)[CH3:8])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 13489605Phenyl 5-tert-butylisoxazol-3-ylcarbamateHCID 59394039[6-(4-Fluoro-2-methyl-1H-indol-5-yloxy)-pyrimidin-4-ylmethyl]-methyl-carbamic acid tert-butyl ester

Product 1

HCID 59394696{6-[1-(5-tert-Butyl-isoxazol-3-ylcarbamoyl)-4-fluoro-2-methyl-1H-indol-5-yloxy]-pyrimidin-4-ylmethyl}-methyl-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of [6-(4-fluoro-2-methyl-1H-indol-5-yloxy)-pyrimidin-4-ylmethyl]-methyl-carbamic acid tert-butyl ester (275 mg, 0.712 mmol) in THF (7 mL), NaH (85 mg, 2.13 mmol) is added under nitrogen at 0° C. The resulting mixture is stirred for 2 h. Then (5-tert-butyl-isoxazol-3-yl)-carbamic acid phenyl ester (370 mg, 1.42 mmol) is added to this mixture. The resulting mixture is allowed to warm to rt and stir for 18 h. The mixture is then quenched with saturated aqueous ammonium chloride. The aqueous phase is extracted with EtOAc (2×). The combined organic layers are washed with brine, dried over anhydrous sodium sulphate, concentrated and purified by FCC (0-70% EtOAc/heptane) to provide the title compound. MS (ESI) m/z 553.1 (M+1).

Workup

  1. stirringstir for 18 h
  2. customThe mixture is then quenched with saturated aqueous ammonium chloride
  3. extractionThe aqueous phase is extracted with EtOAc (2×)
  4. washThe combined organic layers are washed with brine
  5. dry with materialdried over anhydrous sodium sulphate
  6. concentrationconcentrated
  7. custompurified by FCC (0-70% EtOAc/heptane)

Sources & evidence

ORD record
ord-699731bf8d084497a5d936fe1239dfe0
Source dataset
uspto-grants-2013_07
Patent number
US08492393B2

Reaction notes

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