Dichloromethane → 2-(4-(4-ethoxy-6-oxo-1,6-dihydropyridin-3-yl)-2-fluorophenyl)-N-(6-(1, 1,1-trifluoro-2-methylpropan-2-yl)pyridin-3-yl)acetamide hydrochloride

HRID 1050163Notes

Reaction equation

HRID 1050163 reaction equation
Br[C:2]1[CH:7]=[C:6]([C:8]([CH3:14])([CH3:13])[C:9]([F:12])([F:11])[F:10])[N:5]=[CH:4][C:3]=1[NH:15][C:16](=[O:44])[CH2:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]2[CH:25]=[N:26][C:27]([O:33]CC3C=CC(OC)=CC=3)=[CH:28][C:29]=2[O:30][CH2:31][CH3:32])=[CH:20][C:19]=1[F:43].C(Cl)[Cl:46]>[Pd]>[ClH:46].[CH2:31]([O:30][C:29]1[C:24]([C:21]2[CH:22]=[CH:23][C:18]([CH2:17][C:16]([NH:15][C:3]3[CH:4]=[N:5][C:6]([C:8]([CH3:14])([CH3:13])[C:9]([F:11])([F:12])[F:10])=[CH:7][CH:2]=3)=[O:44])=[C:19]([F:43])[CH:20]=2)=[CH:25][NH:26][C:27](=[O:33])[CH:28]=1)[CH3:32]

Participants

4

Reactant 2

HCID 6344DichloromethaneHCID 90423574N-(4-bromo-6-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridin-3-yl)-2-(4-(4-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)acetamide

Product 1

HCID 904233592-(4-(4-ethoxy-6-oxo-1,6-dihydropyridin-3-yl)-2-fluorophenyl)-N-(6-(1, 1,1-trifluoro-2-methylpropan-2-yl)pyridin-3-yl)acetamide hydrochlorideYield 34.6%

Reagents, catalysts & solvents 1

HCID 23938PalladiumCatalyst

Conditions

Temperature
25 °C

Procedure

To a mixture of N-(4-bromo-6-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridin-3-yl)-2-(4-(4-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)acetamide (30 mg, 0.044 mmol) in DCM (10 mL) was added Pd/C (4 mg, 0.038 mmol). The mixture was stirred at 25° C. for 72 h under H2. The mixture was filtered and concentrated. The crude material was purified by preparative HPLC (Column: ASB C18 150*25 mm; Mobile phase A: Water+0.1% HCl; Mobile phaseB: MeCN; Flowrate: 25 mL/min; Gradient Profile Description: 45-75 (B %)) to yield an off-white solid of 2-(4-(4-ethoxy-6-oxo-1,6-dihydropyridin-3-yl)-2-fluorophenyl)-N-(6-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridin-3-yl)acetamide hydrochloride (7.91 mg, 0.015 mmol, 34.6% yield). TLC (DCM/MeOH=9:1, Rf=0.2): 1H NMR (400 MHz, CD3OD): δ 9.08 (d, J=2.0 Hz, 1H), 8.32 (dd, J=2.4, 8.8 Hz, 1H), 7.93 (d, J=8.8 Hz, 1H), 7.81 (s, 1H), 7.44 (t, J=8.0 Hz, 1H), 7.34-7.27 (m, 2H), 6.39 (s, 1H), 4.25 (q, J=7.2 Hz, 2H), 3.89 (s, 2H), 1.69 (s, 6H), 1.41 (t, J=7.2 Hz, 3H). ES-LCMS m/z 478.1 (M+H).

Workup

  1. filtrationThe mixture was filtered
  2. concentrationconcentrated
  3. customThe crude material was purified by preparative HPLC (Column: ASB C18 150*25 mm; Mobile phase A: Water+0.1% HCl; Mobile phaseB: MeCN; Flowrate: 25 mL/min; Gradient Profile Description: 45-75 (B %))

Sources & evidence

ORD record
ord-59e4d9bccb6f4f9a93694b9c996a6995
Source dataset
uspto-grants-2016_07
Patent number
US09382238B2

Reaction notes

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