Water → 4-{[(2S)-2-{[6-(2-Fluorophenyl)-5-(4-methoxyphenyl)furo[2,3-d]pyrimidin-4-yl]oxy}propyl]-(methyl)amino}butyric acid tert.-butyl ester

HRID 1926942Notes

Reaction equation

HRID 1926942 reaction equation
[H-].[Na+].[C:3]([O:7][C:8](=[O:18])[CH2:9][CH2:10][CH2:11][N:12]([CH2:14][C@@H:15]([OH:17])[CH3:16])[CH3:13])([CH3:6])([CH3:5])[CH3:4].Cl[C:20]1[C:21]2[C:28]([C:29]3[CH:34]=[CH:33][C:32]([O:35][CH3:36])=[CH:31][CH:30]=3)=[C:27]([C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=3[F:43])[O:26][C:22]=2[N:23]=[CH:24][N:25]=1.O>C1COCC1.[I-].C([N+](CCCC)(CCCC)CCCC)CCC.C(OCC)(=O)C>[C:3]([O:7][C:8](=[O:18])[CH2:9][CH2:10][CH2:11][N:12]([CH2:14][C@@H:15]([O:17][C:20]1[C:21]2[C:28]([C:29]3[CH:30]=[CH:31][C:32]([O:35][CH3:36])=[CH:33][CH:34]=3)=[C:27]([C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=3[F:43])[O:26][C:22]=2[N:23]=[CH:24][N:25]=1)[CH3:16])[CH3:13])([CH3:4])([CH3:6])[CH3:5]

Participants

8

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 580168704-Chloro-6-(2-fluorophenyl)-5-(4-methoxyphenyl)furo[2,3-d]pyrimidineHCID 580169214-{[(2S)-2-Hydroxypropyl](methyl)amino}butyric acid tert.-butyl ester

Product 1

HCID 580168184-{[(2S)-2-{[6-(2-Fluorophenyl)-5-(4-methoxyphenyl)furo[2,3-d]pyrimidin-4-yl]oxy}propyl]-(methyl)amino}butyric acid tert.-butyl ester

Reagents, catalysts & solvents 3

HCID 67553Tetrabutylammonium IodideCatalystHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Add 22 mg (0.54 mmol) sodium hydride (60% dispersion in mineral oil) to a solution of 100 mg (0.43 mmol) 4-{[(2S)-2-hydroxypropyl](methyl)amino}butyric acid tert.-butyl ester in 1 ml THF, with ice cooling. After stirring for ten minutes with ice cooling, add a solution of 161 mg (0.45 mmol) 4-chloro-6-(2-fluorophenyl)-5-(4-methoxyphenyl)furo[2,3-d]pyrimidine in 2 ml THF and 8 mg (0.02 mmol) tetra-n-butylammonium iodide. Stir the reaction mixture for 16 hours at room temperature. After adding water and ethyl acetate, wash the separated organic phase with 1 N hydrochloric acid and concentrate by vacuum evaporation. Take up the residue in acetonitrile/DMSO and purify by preparative RP-HPLC (gradient: water/acetonitrile). 114 mg (93% purity, 45% of theor.) of the desired product is obtained.

Workup

  1. stirringStir the reaction mixture for 16 hours at room temperature
  2. washwash the separated organic phase with 1 N hydrochloric acid
  3. concentrationconcentrate by vacuum evaporation
  4. custompurify by preparative RP-HPLC (gradient: water/acetonitrile)

Sources & evidence

ORD record
ord-3c51f2a3ae0044969e84097bac89a330
Source dataset
uspto-grants-2012_05
Patent number
US08183246B2

Reaction notes

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