4-Methylmorpholine → HCID 11418466, compound

HRID 1809151Notes

Reaction equation

HRID 1809151 reaction equation
[CH3:1][C:2]1[N:6]([C:7]2[CH:8]=[C:9]([CH:15]=[CH:16][CH:17]=2)[O:10][CH2:11][C:12]([OH:14])=O)[N:5]=[N:4][N:3]=1.Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.CN1CCOCC1.[NH2:47][C:48]1[CH:49]=[CH:50][C:51]([Cl:58])=[C:52]([C:54]([F:57])([F:56])[F:55])[CH:53]=1>C(OCC)(=O)C.CN(C=O)C>[Cl:58][C:51]1[CH:50]=[CH:49][C:48]([NH:47][C:12](=[O:14])[CH2:11][O:10][C:9]2[CH:15]=[CH:16][CH:17]=[C:7]([N:6]3[C:2]([CH3:1])=[N:3][N:4]=[N:5]3)[CH:8]=2)=[CH:53][C:52]=1[C:54]([F:55])([F:56])[F:57]

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 675744-Chloro-3-(trifluoromethyl)anilineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 549129832-[3-(5-Methyl-1H-tetrazol-1-yl)phenoxy]acetic acid

Product 1

HCID 11418466HCID 11418466, compoundYield 5.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a 25 mL recovery flask was added [3-(5-methyl-tetrazol-1-yl)-phenoxy]-acetic acid 16 (424 mg, 1.81 mmol, 1.0 eq.) and a stirbar. 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (521 mg, 2.72 mmol, 1.5 eq.) and 1-hydroxybenzotriazole (367 mg, 2.72 mmol, 1.5 eq.) were added to the flask. DMF (12 mL) and N-methylmorpholine (611 μL, 5.44 mmol, 3.0 eq.) were added to the reaction flask. The mixture was allowed to stir for 30 min at room temperature. 5-Amino-2-chlorobenzotrifluoride (709 mg, 3.62 mmol, 2.0 eq.) was added to the flask and the resulting mixture was allowed to stir overnight at room temperature. The reaction mixture was diluted with ethyl acetate (100 mL) and washed with a succession of H2O (1×50 mL), 10% aq. LiCl (3×50 mL), and sat'd aq. NaCl (1×50 mL). The aqueous phases were combined and extracted with ethyl acetate (2×30 mL). The combined organic phases were dried over anhydrous Na2SO4, filtered, concentrated and purified by flash chromatography to yield an off-white solid (40 mg, 5%). LC/MSD (HP Series 1100 MSD) MS (ES+) m/z 412.0 (M+H)+1 1H-NMR, Varian 400 MHz (DMSO-d6) δ 10.55 (s, 1H), 8.21 (d, 1H), 7.92-7.89 (m, 1H), 7.70-7.68 (m, 1H), 7.57 (t, 1H), 7.36-7.35 (m, 1H), 7.29-7.27 (m, 2H), 4.85 (s, 2H), 2.53 (s, 3H) ppm.

Workup

  1. stirringto stir overnight at room temperature
  2. washwashed with a succession of H2O (1×50 mL), 10% aq. LiCl (3×50 mL)
  3. extractionextracted with ethyl acetate (2×30 mL)
  4. dry with materialThe combined organic phases were dried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custompurified by flash chromatography

Sources & evidence

ORD record
ord-264d775ab3ae444e81f67ea42de57b4b
Source dataset
uspto-grants-2013_01
Patent number
US08362017B2

Reaction notes

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