Water → HCID 90416401, compound

HRID 1428552Notes

Reaction equation

HRID 1428552 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-42a40ff7ac464311b6aa686c9e37e326
Source dataset
uspto-grants-2015_01
Patent number
US08937071B2

Reaction notes

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