Hydrochloric Acid → HCID 66613795, compound

HRID 510136Notes

Reaction equation

HRID 510136 reaction equation
[C:1]([C:4]1[N:12]=[C:11]([C:13]2[C:21]3[C:16](=[N:17][CH:18]=[CH:19][CH:20]=3)[N:15]([CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=3[F:29])[N:14]=2)[N:10]=[C:9]2[C:5]=1[N:6]([CH3:31])[C:7](=[O:30])[NH:8]2)(=[O:3])[CH3:2].[CH3:32][Mg]Br.Cl>O1CCCC1.C(OCC)C>[F:29][C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=1[CH2:22][N:15]1[C:16]2=[N:17][CH:18]=[CH:19][CH:20]=[C:21]2[C:13]([C:11]2[N:10]=[C:9]3[C:5]([N:6]([CH3:31])[C:7](=[O:30])[NH:8]3)=[C:4]([C:1]([OH:3])([CH3:32])[CH3:2])[N:12]=2)=[N:14]1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 66614330HCID 66614330, compoundHCID 178418573HCID 178418573, compound2×

Product 1

HCID 66613795HCID 66613795, compound

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

237 mg (0.568 mmol) of the compound obtained in example 134 in tetrahydrofuran were cooled to 0° C. and admixed with 0.568 ml of a 3M solution of methylmagnesium bromide in diethyl ether, and the mixture was stirred at this temperature for 1 h and then at RT overnight. Then 2 portions, each of 0.379 ml, of a 3M solution of methylmagnesium bromide in diethyl ether were added and the mixture was stirred at RT for a further night. After cooling, first ice and then 4N hydrochloric acid (20 ml) were added and the mixture was stirred vigorously. The mixture was then extracted three times with ethyl acetate and the combined organic phases were washed with saturated aqueous sodium chloride solution. After drying over sodium sulfate, the mixture was filtered and concentrated, and the residue was purified by means of preparative HPLC (acetonitrile:water (+0.05% formic acid) gradient). 29 mg of the title compound were obtained (10% of theory).

Workup

  1. customat RT
  2. customovernight
  3. stirringthe mixture was stirred at RT for a further night
  4. temperatureAfter cooling
  5. stirringthe mixture was stirred vigorously
  6. extractionThe mixture was then extracted three times with ethyl acetate
  7. washthe combined organic phases were washed with saturated aqueous sodium chloride solution
  8. dry with materialAfter drying over sodium sulfate
  9. filtrationthe mixture was filtered
  10. concentrationconcentrated
  11. customthe residue was purified by means of preparative HPLC (acetonitrile:water (+0.05% formic acid) gradient)

Sources & evidence

ORD record
ord-b5ea4ab81c2b4d6da4ced10157f81d7a
Source dataset
uspto-grants-2015_08
Patent number
US09096592B2

Reaction notes

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