Methyl chloroformate → HCID 90387596, compound

HRID 874464Notes

Reaction equation

HRID 874464 reaction equation
[CH3:1][N:2]1[C:15]2[C:6]([CH:7]=[CH:8][C:9]3[NH:19][CH2:18][CH:17]=[C:11]4[NH:12][C:13](=[O:16])[C:14]=2[C:10]=34)=[C:5]([CH2:20][S:21]([CH3:24])(=[O:23])=[O:22])[CH:4]=[CH:3]1.[C:25](Cl)(=[O:28])[O:26][CH3:27].C(N(C(C)C)C(C)C)C.C(=O)([O-])[O-].[Na+].[Na+]>CN(C)C(=O)C.CO>[CH3:1][N:2]1[C:15]2[C:6]([CH:7]=[CH:8][C:9]3[N:19]([C:25]([O:26][CH3:27])=[O:28])[CH2:18][CH:17]=[C:11]4[NH:12][C:13](=[O:16])[C:14]=2[C:10]=34)=[C:5]([CH2:20][S:21]([CH3:24])(=[O:23])=[O:22])[CH:4]=[CH:3]1

Participants

7

Reactant 4

HCID 6586Methyl chloroformateHCID 10340Sodium CarbonateHCID 81531DiisopropylethylamineHCID 90387726HCID 90387726, compound

Product 1

HCID 90387596HCID 90387596, compoundYield 40.9%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 31374DimethylacetamideSolvent

Procedure

A mixture of Example 6a (0.0145 g, 0.042 mmol) in N,N-dimethylacetamide (0.5 mL) was treated sequentially with methyl carbonochloridate (0.016 mL, 0.211 mmol) and N-ethyl-N-isopropylpropan-2-amine (0.074 mL, 0.422 mmol) and stirred overnight at ambient temperature. The reaction mixture was then diluted with methanol (1.2 mL), treated with sodium carbonate (0.011 g, 0.105 mmol) and stirred at ambient temperature for 4 hours. The reaction mixture was partitioned between ethyl acetate and water and washed with saturated aqueous sodium chloride. The aqueous layers were combined and exhaustedly extracted with ethyl acetate. The combined organic layers were dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was purified by reverse phase HPLC(C18, acetonitrile/water (0.1% TFA), 0-50%) to provide 0.0069 g (40.7%) of the title compound. 1H NMR (400 MHz, DMSO-d6) δ 10.51 (s, 1H), 7.76 (d, J=1.53 Hz, 1H), 7.69 (s, 1H), 7.29 (m, 1H), 7.23 (m, 1H), 6.79 (s, 1H), 5.00 (d, J=15.56 Hz, 1H), 4.44 (m, 2H), 4.12 (s, 3H), 3.94 (d, J=15.26 Hz, 1H), 3.50 (s, 3H), 2.93 (s, 3H). MS (ESI+) m/z 402.1 (M+H)+.

Workup

  1. stirringstirred at ambient temperature for 4 hours
  2. customThe reaction mixture was partitioned between ethyl acetate and water
  3. washwashed with saturated aqueous sodium chloride
  4. extractionexhaustedly extracted with ethyl acetate
  5. dry with materialThe combined organic layers were dried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by reverse phase HPLC(C18, acetonitrile/water (0.1% TFA), 0-50%)

Sources & evidence

ORD record
ord-0efce6fc9b6b43eca3cab4dd8467c21a
Source dataset
uspto-grants-2015_03
Patent number
US08980879B2

Reaction notes

Loading…