Ammonium Chloride → HCID 90202341, compound

HRID 929783Notes

Reaction equation

HRID 929783 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:21]=[CH:22][CH:23]=1)[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH:17]=[C:16]([C:18](O)=[O:19])[O:15][N:14]=2)=[CH:9][CH:8]=1.C([N:27](C(C)C)CC)(C)C.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.[NH4+].[Cl-]>C(Cl)Cl.CN(C=O)C>[F:1][C:2]1[CH:3]=[C:4]([CH:21]=[CH:22][CH:23]=1)[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH:17]=[C:16]([C:18]([NH2:27])=[O:19])[O:15][N:14]=2)=[CH:9][CH:8]=1

Participants

8

Reactant 5

HCID 25517Ammonium Chloride2×HCID 757711-Hydroxybenzotriazole2×HCID 81531Diisopropylethylamine2×HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride2×HCID 90202470HCID 90202470, compound2×

Product 1

HCID 90202341HCID 90202341, compoundYield 21%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

3-[4-(3-Fluoro-benzyloxy)-phenyl]-isoxazole-5-carboxylic acid (which may be prepared as described in Preparation of Intermediate 5; 313 mg, 1.0 mmol) and diisopropylethylamine (275 μL, 1.6 mmol) were dissolved in CH2Cl2 (6 mL). N′-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride (160 mg, 3 mmol), 1-hydroxybenzotriazole (180 mg, 1.16 mmol), and NH4Cl (53.5 mg, 3 mmol) were added. The reaction mixture was stirred at room temperature. DMF (6 mL) was added to the heterogeneous reaction mixture and the resulting solution was stirred at room temperature for 48 h. Additional equivalents of NH4Cl, 1-hydroxybenzotriazole, N′-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride, and diisopropylethylamine were added. The reaction mixture was stirred for an additional 48 h, and then purified by chromatography, eluting with 45% EtOAc/hexanes, to give 3-[4-(3-fluoro-benzyloxy)-phenyl]-isoxazole-5-carboxylic acid amide (65 mg, 21%), mp 221-222° C. LRMS (ESI+): m/z [M+H]+ 313.0. Impurity observed at m/z=423. 1H NMR (300 MHz, DMSO-d6) δ ppm 8.34 (s, 1H), 7.98 (s, 1H), 7.84 (d, J=9.2 Hz, 2H), 7.52 (s, 1H), 7.42 (dd, J=8.1, 5.9 Hz, 1H), 7.29 (d, J=7.3 Hz, 2H), 7.15 (d, J=8.8 Hz, 3H), 5.20 (s, 2H).

Workup

  1. stirringthe resulting solution was stirred at room temperature for 48 h
  2. stirringThe reaction mixture was stirred for an additional 48 h
  3. custompurified by chromatography
  4. washeluting with 45% EtOAc/hexanes

Sources & evidence

ORD record
ord-9de9006016dc4234979d79b76a79214f
Source dataset
uspto-grants-2016_03
Patent number
US09296711B2

Reaction notes

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