1,2-Dichloroethane → 2-{[(2,4-Difluorophenyl)methyl]oxy}-N-(3-methyl-4-isoxazolyl)-5-(4-morpholinylcarbonyl)benzamide

HRID 1623863Notes

Reaction equation

HRID 1623863 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH2:9][O:10][C:11]1[CH:20]=[CH:19][C:18]([C:21]([N:23]2[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)=[O:22])=[CH:17][C:12]=1[C:13](OC)=[O:14].[OH-].[Li+].Cl.Cl.[CH3:33][C:34]1[C:38]([NH2:39])=[CH:37][O:36][N:35]=1.ON1C2N=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.C(Cl)CCl>O1CCCC1.O>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH2:9][O:10][C:11]1[CH:20]=[CH:19][C:18]([C:21]([N:23]2[CH2:24][CH2:25][O:26][CH2:27][CH2:28]2)=[O:22])=[CH:17][C:12]=1[C:13]([NH:39][C:38]1[C:34]([CH3:33])=[N:35][O:36][CH:37]=1)=[O:14]

Participants

10

Reactant 7

HCID 111,2-DichloroethaneHCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 138042853-Methyl-1,2-oxazol-4-amine hydrochlorideHCID 67107388Methyl 2-([(2,4-difluorophenyl)methyl]oxy}-5-(4-morpholinylcarbonyl)benzoate

Product 1

HCID 671077722-{[(2,4-Difluorophenyl)methyl]oxy}-N-(3-methyl-4-isoxazolyl)-5-(4-morpholinylcarbonyl)benzamide

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of methyl 2-{[(2,4-difluorophenyl)methyl]oxy}-5-(4-morpholinylcarbonyl)benzoate acid (may be prepared as described in Description 110; 100 mg, 0.26 mmol) in tetrahydrofuran (4 ml) was added lithium hydroxide (26 mg, 109 mmol) and water (1 ml). The mixture was heated at 50° C. for one hour, cooled and 2 M hydrochloric acid (0.54 ml, 1.09 mmol) was added. The solvent was removed in vacuo and the residue was redissolved in N,N-dimethylformamide (5 ml). 3-Methyl-4-isoxazolamine hydrochloride (42.8 mg, 0.32 mmol), 1-hydroxy-7-azabenzotriazole (39.7 mg, 0.29 mmol), diisopropylethylamine (0.09 ml, 0.53 mmol) and EDC (76 mg, 0.40 mmol) were added. The solution was stirred for 18 hours. Water (3 ml) was added and a pale brown solid precipitated which was filtered. Recrystallisation with 1:1 methanol/DMSO yielded the title compound as a white solid. 9.5 mg.

Workup

  1. temperaturecooled
  2. customThe solvent was removed in vacuo
  3. dissolutionthe residue was redissolved in N,N-dimethylformamide (5 ml)
  4. customa pale brown solid precipitated which
  5. filtrationwas filtered
  6. customRecrystallisation with 1:1 methanol/DMSO

Sources & evidence

ORD record
ord-d1a80a6e38fa45028a02e3fdf6f0d9fe
Source dataset
uspto-grants-2014_07
Patent number
US08778939B2

Reaction notes

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