Methyl chloroformate → HCID 68821818, compound

HRID 736381Notes

Reaction equation

HRID 736381 reaction equation
[NH2:1][C:2]1[C:3]([C:8]2[CH:26]=[CH:25][C:11]([C:12]([NH:14][C:15]3[CH:20]=[CH:19][C:18]([C:21]([CH3:24])([CH3:23])[CH3:22])=[CH:17][CH:16]=3)=[O:13])=[CH:10][CH:9]=2)=[N:4][CH:5]=[CH:6][CH:7]=1.Cl[C:28]([O:30][CH3:31])=[O:29].C([O-])([O-])=O.[K+].[K+]>COCCOC>[C:21]([C:18]1[CH:19]=[CH:20][C:15]([NH:14][C:12]([C:11]2[CH:10]=[CH:9][C:8]([C:3]3[C:2]([NH:1][C:28](=[O:29])[O:30][CH3:31])=[CH:7][CH:6]=[CH:5][N:4]=3)=[CH:26][CH:25]=2)=[O:13])=[CH:16][CH:17]=1)([CH3:22])([CH3:23])[CH3:24]

Participants

5

Reactant 3

HCID 6586Methyl chloroformateHCID 11430Potassium CarbonateHCID 10382943HCID 10382943, compound

Product 1

HCID 68821818HCID 68821818, compound

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Procedure

The product from Example 3 (500 mg, 1.45 mmol), methyl chloroformate (0.43 mL, 5.56 mmol), and K2CO3 (1.15 g, 8.33 mmol) were heated in DME (8 mL) at 65° C. for 24 hours. The mixture was allowed to cool to room temperature, concentrated under reduced pressure, and the residue was taken up in ethyl acetate (50 mL). The ethyl acetate was washed with H2O (3×15 mL) and brine (15 mL), dried over Na2SO4, filtered, and the filtrate concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (eluant gradient from 99:1 CH2Cl2:CH3OH to 95:5 CH2Cl2:CH3OH) to provide the title compound as a solid. 1H NMR (300 MHz, DMSO-d6) δ 10.24 (s, 1H), 9.15 (s, 1H), 8.53 (dd, J=4.5 Hz, 1.6 Hz, 1H), 8.02-8.05 (m, 2H), 7.88 (dd, J=8.1 Hz, 1.4 Hz, 1H), 7.70-7.77 (m, 4H), 7.35-7.46 (m, 3H), 3.55 (s, 3H), 1.29 (s, 9H); MS (ESI+) m/z 404 (M+H)+.

Workup

  1. concentrationconcentrated under reduced pressure
  2. washThe ethyl acetate was washed with H2O (3×15 mL) and brine (15 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationthe filtrate concentrated under reduced pressure
  6. customThe residue was purified by column chromatography on silica gel (eluant gradient from 99:1 CH2Cl2:CH3OH to 95:5 CH2Cl2:CH3OH)

Sources & evidence

ORD record
ord-eb032b96a19d4b64b20c675369100a8b
Source dataset
uspto-grants-2009_09
Patent number
US07595332B2

Reaction notes

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