HCID 57955163, compound → HCID 57955266, compound

HRID 73699Notes

Reaction equation

HRID 73699 reaction equation
[CH3:1][Mg]Br.[NH2:4][C:5]1[C:10]2=[C:11]([C:28]3[CH:33]=[CH:32][C:31]([NH:34][C:35]([NH:37][C:38]4[CH:43]=[C:42]([C:44]([F:47])([F:46])[F:45])[CH:41]=[CH:40][N:39]=4)=[O:36])=[CH:30][CH:29]=3)[C:12]([C:22](N(OC)C)=[O:23])=[C:13]([CH2:14][N:15]3[CH2:20][CH2:19][N:18]([CH3:21])[CH2:17][CH2:16]3)[N:9]2[N:8]=[CH:7][N:6]=1>C1COCC1>[C:22]([C:12]1[C:11]([C:28]2[CH:29]=[CH:30][C:31]([NH:34][C:35]([NH:37][C:38]3[CH:43]=[C:42]([C:44]([F:45])([F:47])[F:46])[CH:41]=[CH:40][N:39]=3)=[O:36])=[CH:32][CH:33]=2)=[C:10]2[N:9]([C:13]=1[CH2:14][N:15]1[CH2:20][CH2:19][N:18]([CH3:21])[CH2:17][CH2:16]1)[N:8]=[CH:7][N:6]=[C:5]2[NH2:4])(=[O:23])[CH3:1]

Participants

4

Reactant 2

HCID 57955163HCID 57955163, compoundHCID 178418573HCID 178418573, compound

Product 1

HCID 57955266HCID 57955266, compoundYield 42.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

Methyl magnesium bromide (0.54 mL, 1.63 mmol, in 3.0 M in diethyl ether) was added dropwise to a stirring solution of Example 94 (100.0 mg, 0.163 mmol) in THF (2 mL) at rt. The reaction was heated to 60° C. and allowed to stir overnight (15 hrs) or until all starting material had been consumed as seen by HPLC. After cooling to rt, the reaction was quenched with methanol and diluted with 100 mL of EtOAc and washed 3× with saturated NH4Cl solution. The organic layer was dried over Na2SO4, concentrated and purified by HPLC (10-70% ACN/H2O) to give 37.9 mg (0.07 mmol, 40.9%) of the title compound. 1H-NMR (DMSO-d6). δ 10.88 (s, 1H), 10.19 (s, 1H), 8.57 (d, J=5.4 Hz, 1H), 8.27 (s, 1H), 8.03 (s, 1H), 7.70 (d, J=8.1 Hz, 2H), 7.40-7.35 (m, 3H), 4.17 (s, 2H), 3.08-3.04 (m, 4H), 2.73-2.65 (m, 7H), 2.06 (s, 3H). MS [M+H]+=568; LCMS RT=2.31 min.

Workup

  1. customuntil all starting material had been consumed
  2. temperatureAfter cooling to rt
  3. customthe reaction was quenched with methanol
  4. additiondiluted with 100 mL of EtOAc
  5. washwashed 3× with saturated NH4Cl solution
  6. dry with materialThe organic layer was dried over Na2SO4
  7. concentrationconcentrated
  8. custompurified by HPLC (10-70% ACN/H2O)

Sources & evidence

ORD record
ord-08ea6ef62e88445ea61395fd953529e2
Source dataset
uspto-grants-2014_09
Patent number
US08829185B2

Reaction notes

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