Ethylamine → HCID 22050456, compound

HRID 1867157Notes

Reaction equation

HRID 1867157 reaction equation
[Br:1][C:2]1[C:3](=[O:31])[N:4]([C:23]2[C:28]([F:29])=[CH:27][CH:26]=[CH:25][C:24]=2[F:30])[C:5]([CH3:22])=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:20]=[CH:19][C:18]([F:21])=[CH:17][C:11]=1[O:12][CH2:13][C:14](O)=[O:15].C[N:33]1CCO[CH2:35][CH2:34]1.ClC(OCC(C)C)=O.C(N)C>CC(N(C)C)=O>[Br:1][C:2]1[C:3](=[O:31])[N:4]([C:23]2[C:28]([F:29])=[CH:27][CH:26]=[CH:25][C:24]=2[F:30])[C:5]([CH3:22])=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:20]=[CH:19][C:18]([F:21])=[CH:17][C:11]=1[O:12][CH2:13][C:14]([NH:33][CH2:34][CH3:35])=[O:15]

Participants

6

Reactant 4

HCID 6341EthylamineHCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 22050560HCID 22050560, compound

Product 1

HCID 22050456HCID 22050456, compoundYield 51%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

To a cooled (−10° C.) solution of [2-({[3-bromo-1-(2,6-difluorophenyl)-6-methyl-2-oxo-1,2-dihydropyridin-4-yl]oxy}methyl)-5-fluorophenoxy]acetic acid (from Step 4) (0.15 g, 0.30 mmol) in DMA (2.0 mL) was added 4-methylmorpholine (0.04 mL, 0.36 mmol) and isobutyl chloroformate (0.05 mL, 0.36 mmol). Ethylamine (0.04 mL, 0.45 mmol) was added after 20 minutes. DMF removed by distillation after 1 h. Crude product purified by preparatory HPLC. Acetonitrile was evaporated and the solution washed with 5% NaHCO3 (30 mL) and extracted in DCM (3×25 mL). The organic extracts were dried over Na2SO4, filtered, concentrated, and dried in vacuo to give a white solid (0.080 g, 51%). 1H NMR (CD3OD/400 MHz) δ7.60 (m, 1H), 7.53 (t, 1H, J=8.0 Hz), 7.23 (t, 2H, J=8.4 Hz), 6.82 (m, 2H), 6.71 (s, 1H), 5.42 (s, 2H), 4.61 (s, 2H), 3.31 (q, 2H, J=6.4 Hz), 2.10 (s, 3H), 1.09 (t, 3H, J=7.2 Hz). ESHRMS m/z 525.0616 and 527.0568 (M+H calculated for C23H21BrF3N2O4 requires 525.0631 and 527.0614).

Workup

  1. customDMF removed by distillation after 1 h
  2. customCrude product purified by preparatory HPLC
  3. customAcetonitrile was evaporated
  4. washthe solution washed with 5% NaHCO3 (30 mL)
  5. extractionextracted in DCM (3×25 mL)
  6. dry with materialThe organic extracts were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customdried in vacuo

Sources & evidence

ORD record
ord-d1e1798b4f8a42168652e1bd14453cd2
Source dataset
uspto-grants-2009_12
Patent number
US07629363B2

Reaction notes

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