Water → 2-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridine-3-yl)-2-fluorophenyl)-N-(3-(3-methyl-1H-pyrazol-1-yl)-5-(trifluoromethyl)phenyl)acetamide

HRID 1050152Notes

Reaction equation

HRID 1050152 reaction equation
[CH3:1][C:2]1[CH:6]=[CH:5][N:4]([C:7]2[CH:8]=[C:9]([CH:11]=[C:12]([C:14]([F:17])([F:16])[F:15])[CH:13]=2)[NH2:10])[N:3]=1.[CH2:18]([O:20][C:21]1[CH:22]=[C:23]([C:37]2[CH:42]=[CH:41][C:40]([CH2:43][C:44](O)=[O:45])=[C:39]([F:47])[CH:38]=2)[CH:24]=[N:25][C:26]=1[O:27][CH2:28][C:29]1[CH:34]=[CH:33][C:32]([O:35][CH3:36])=[CH:31][CH:30]=1)[CH3:19].C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC.O>N1C=CC=CC=1>[CH2:18]([O:20][C:21]1[CH:22]=[C:23]([C:37]2[CH:42]=[CH:41][C:40]([CH2:43][C:44]([NH:10][C:9]3[CH:11]=[C:12]([C:14]([F:15])([F:17])[F:16])[CH:13]=[C:7]([N:4]4[CH:5]=[CH:6][C:2]([CH3:1])=[N:3]4)[CH:8]=3)=[O:45])=[C:39]([F:47])[CH:38]=2)[CH:24]=[N:25][C:26]=1[O:27][CH2:28][C:29]1[CH:30]=[CH:31][C:32]([O:35][CH3:36])=[CH:33][CH:34]=1)[CH3:19]

Participants

6

Reactant 4

HCID 962WaterHCID 111923Propylphosphonic anhydrideHCID 790184503-(3-methyl-1H-pyrazol-1-yl)-5-(trifluoromethyl)anilineHCID 904166242-(4-(5-Ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl) acetic acid

Product 1

HCID 904231052-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridine-3-yl)-2-fluorophenyl)-N-(3-(3-methyl-1H-pyrazol-1-yl)-5-(trifluoromethyl)phenyl)acetamideYield 34.5%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
16 °C

Procedure

To a solution of 3-(3-methyl-1H-pyrazol-1-yl)-5-(trifluoromethyl)aniline (250 mg, 1.036 mmol) and 2-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)acetic acid (429 mg, 1.036 mmol) in pyridine (5 mL) was added T3P® (3298 mg, 5.18 mmol) in portions. The mixture was stirred at 16° C. for 1 h. LCMS analysis showed the starting material disappeared. 10 mL of water was added dropwise into the reaction solution and then the mixture was filtered. The filter cake was washed with water (20 mL) and dried in vacuo to afford pure product 2-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridine-3-yl)-2-fluorophenyl)-N-(3-(3-methyl-1H-pyrazol-1-yl)-5-(trifluoromethyl)phenyl)acetamide (280 mg, 0.357 mmol, 34.5% yield). 1H NMR (400 MHz, CD3OD): δ 8.25 (s, 1H), 8.15 (d, J=2.6 Hz, 1H), 7.96 (d, J=2.0 Hz, 1H), 7.85 (s, 1H), 7.75 (s, 1H), 7.50-7.43 (m, 3H), 7.41 (d, J=9.0 Hz, 3H), 6.92 (d, J=8.8 Hz, 2H), 6.36 (d, J=2.4 Hz, 1H), 5.37 (s, 2H), 4.18-4.13 (m, 2H), 3.86 (s, 2H), 3.79 (s, 3H), 2.34 (s, 3H), 1.43 (t, J=7.0 Hz, 3H). ES-LCMS: m/z 635.1 (M+H).

Workup

  1. filtrationthe mixture was filtered
  2. washThe filter cake was washed with water (20 mL)
  3. customdried in vacuo

Sources & evidence

ORD record
ord-840171a8d0214753b4319c61c15ed3e9
Source dataset
uspto-grants-2016_07
Patent number
US09382238B2

Reaction notes

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