Water → HCID 90416401, compound

HRID 1050022Notes

Reaction equation

HRID 1050022 reaction equation
[C:1]([C:4]1[N:9]=[CH:8][C:7]([NH:10][C:11](=[O:39])[CH2:12][C:13]2[CH:18]=[CH:17][C:16]([C:19]3[CH:20]=[N:21][C:22]([O:28][CH2:29][C:30]4[CH:35]=[CH:34][C:33]([O:36][CH3:37])=[CH:32][CH:31]=4)=[C:23]([O:25][CH2:26][CH3:27])[CH:24]=3)=[CH:15][C:14]=2[F:38])=[CH:6][C:5]=1[C:40]([F:43])([F:42])[F:41])(=[O:3])[CH3:2].[CH3:44][Mg]Br.O>C1COCC1>[CH2:26]([O:25][C:23]1[CH:24]=[C:19]([C:16]2[CH:17]=[CH:18][C:13]([CH2:12][C:11]([NH:10][C:7]3[CH:8]=[N:9][C:4]([C:1]([OH:3])([CH3:44])[CH3:2])=[C:5]([C:40]([F:41])([F:43])[F:42])[CH:6]=3)=[O:39])=[C:14]([F:38])[CH:15]=2)[CH:20]=[N:21][C:22]=1[O:28][CH2:29][C:30]1[CH:31]=[CH:32][C:33]([O:36][CH3:37])=[CH:34][CH:35]=1)[CH3:27]

Participants

5

Reactant 3

HCID 962WaterHCID 90416024HCID 90416024, compoundHCID 178418573HCID 178418573, compound

Product 1

HCID 90416401HCID 90416401, compoundYield 51.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a mixture of N-(6-acetyl-5-(trifluoromethyl)pyridin-3-yl)-2-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)acetamide (100 mg, 0.167 mmol) in THF (10 mL) was added methylmagnesium bromide (0.167 mL, 0.502 mmol). The mixture was stirred at 0° C. for 2 h under a N2 atmosphere. Then the mixture was added to H2O and extracted with EA. The combined organic extract was washed with brine, dried over MgSO4, filtered and concentrated. The crude material was purified by preparative TLC (DCM/MeOH=15:1, Rf=0.6) to yield a yellow solid of 2-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)-N-(6-(2-hydroxypropan-2-yl)-5-(trifluoromethyl)pyridin-3-yl)acetamide (70 mg, 0.086 mmol, 51.1% yield): 1H NMR (400 MHz, CD3OD) δ 8.87 (d, J=2.0 Hz, 1H), 8.45 (d, J=2.0 Hz, 1H), 8.09 (d, J=2.4 Hz, 1H), 7.94 (d, J=2.0 Hz, 1H), 7.44-7.40 (m, 3H), 7.29 (d, J=2.4 Hz, 1H), 6.88 (s, 2H) 6.78 (d, J=2.4 Hz, 1H), 5.35 (s, 2H), 4.17-4.11 (m, 2H), 3.83 (s, 2H), 3.77 (s, 3H), 1.59 (s, 6H), 1.41 (t, J=7.1 Hz, 3H); ES-LCMS m/z 494.2 (M-PMB+H).

Workup

  1. extractionextracted with EA
  2. extractionThe combined organic extract
  3. washwas washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude material was purified by preparative TLC (DCM/MeOH=15:1, Rf=0.6)

Sources & evidence

ORD record
ord-f74407a8d17d40928f6d89ad0e67f675
Source dataset
uspto-grants-2016_07
Patent number
US09382238B2

Reaction notes

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