Hydrochloric Acid → HCID 89657375, compound

HRID 930925Notes

Reaction equation

HRID 930925 reaction equation
[F:1][C:2]1[CH:34]=[C:33]([F:35])[CH:32]=[CH:31][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][C:8]([S:11]([CH3:14])(=[O:13])=[O:12])=[CH:7][C:6]=1[C:15]1[C:16]2[CH:25]=[C:24](C(OCC)=O)[NH:23][C:17]=2[C:18](=[O:22])[N:19]([CH3:21])[CH:20]=1.C[Mg]Br.Cl.O1C[CH2:43][CH2:42][CH2:41]1>>[F:1][C:2]1[CH:34]=[C:33]([F:35])[CH:32]=[CH:31][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][C:8]([S:11]([CH3:14])(=[O:13])=[O:12])=[CH:7][C:6]=1[C:15]1[C:16]2[CH:25]=[C:24]([C:42]([CH3:43])=[CH2:41])[NH:23][C:17]=2[C:18](=[O:22])[N:19]([CH3:21])[CH:20]=1

Participants

5

Reactant 4

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 89657495HCID 89657495, compoundHCID 178418573HCID 178418573, compound

Product 1

HCID 89657375HCID 89657375, compoundYield 25%

Conditions

Temperature
0 °C

Procedure

To a solution of Example 252f (0.10 g, 0.20 mmol) in tetrahydrofuran (6 mL) stirring at 0° C. was added methylmagnesium bromide (0.498 mL, 0.498 mmol). The reaction mixture was stirred at 0° C. for 1 hour, and then aqueous HCl (1 M, 2 mL) was added. The reaction mixture was concentrated and partitioned between saturated aqueous sodium chloride (10 mL) and ethyl acetate. The organic phase was washed with saturated aqueous sodium chloride (30 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by reverse phase-HPLC (C 18 40-90% gradient acetonitrile:water (0.1% TFA)) to provide the title compound (25 mg, 25% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 12.05 (s, 1H), 7.98 (d, J=2.4 Hz, 1H), 7.87 (dd, J=8.7, 2.4 Hz, 1H), 7.61-7.36 (m, 3H), 7.18 (t, J=8.6 Hz, 1H), 6.98 (d, J=8.3 Hz, 1H), 6.34 (d, J=2.2 Hz, 1H), 5.85 (s, 1H), 5.07 (s, 1H), 3.60 (s, 3H), 3.26 (s, 3H), 2.02 (s, 3H). MS (ESI+) m/z 471.1 (M+1)+.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. custompartitioned between saturated aqueous sodium chloride (10 mL) and ethyl acetate
  3. washThe organic phase was washed with saturated aqueous sodium chloride (30 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by reverse phase-HPLC (C 18 40-90% gradient acetonitrile:water (0.1% TFA))

Sources & evidence

ORD record
ord-bd86653c48ec4ba5a6d515736676f9a8
Source dataset
uspto-grants-2016_03
Patent number
US09296741B2

Reaction notes

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