Ethyl Acetate → 2-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)-N-(1-methyl-3-(1, 1,1-trifluoro-2-methylpropan-2-yl)-1H-pyrazol-5-yl)acetamide

HRID 1050174Notes

Reaction equation

HRID 1050174 reaction equation
[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([C:20]2[CH:25]=[CH:24][C:23]([CH2:26][C:27](O)=[O:28])=[C:22]([F:30])[CH:21]=2)[CH:7]=[N:8][C:9]=1[O:10][CH2:11][C:12]1[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=1)[CH3:2].[CH3:31][N:32]1[C:36]([NH2:37])=[CH:35][C:34]([C:38]([CH3:44])([CH3:43])[C:39]([F:42])([F:41])[F:40])=[N:33]1.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC.CC(=O)OCC>N1C=CC=CC=1.O.C(Cl)Cl>[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([C:20]2[CH:25]=[CH:24][C:23]([CH2:26][C:27]([NH:37][C:36]3[N:32]([CH3:31])[N:33]=[C:34]([C:38]([CH3:44])([CH3:43])[C:39]([F:41])([F:40])[F:42])[CH:35]=3)=[O:28])=[C:22]([F:30])[CH:21]=2)[CH:7]=[N:8][C:9]=1[O:10][CH2:11][C:12]1[CH:13]=[CH:14][C:15]([O:18][CH3:19])=[CH:16][CH:17]=1)[CH3:2]

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 111923Propylphosphonic anhydrideHCID 904166242-(4-(5-Ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl) acetic acidHCID 904232181-methyl-3-(1,1,1-trifluoro-2-methylpropan-2-yl)-1H-pyrazol-5-amine

Product 1

HCID 904227162-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)-N-(1-methyl-3-(1, 1,1-trifluoro-2-methylpropan-2-yl)-1H-pyrazol-5-yl)acetamideYield 61.7%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Procedure

To a mixture of 2-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)acetic acid (150 mg, 0.365 mmol), 1-methyl-3-(1,1,1-trifluoro-2-methylpropan-2-yl)-1H-pyrazol-5-amine (83 mg, 0.401 mmol) in pyridine (3 mL) was added T3P® (EA solvate) (0.3 mL, 0.365 mmol) at 25° C. Then the mixture was stirred for 2 h, the mixture was concentrated to give the residue which was distributed between DCM (20 mL) and H2O (10 mL) and extracted with DCM (20 mL×2). The combined organic extracts were washed with brine (20 mL), dried over Na2SO4, filtered and concentrated to yield a white solid of 2-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)-N-(1-methyl-3-(1,1,1-trifluoro-2-methylpropan-2-yl)-1H-pyrazol-5-yl)acetamide (150 mg, 0.225 mmol, 61.7% yield): 1H NMR (400 MHz, CD3OD) δ 8.52 (d, J=4.4 Hz, 1H), 7.94 (d, J=2.0 Hz, 1H), 7.44-7.41 (m, 3H), 7.39 (d, J=8.8 Hz, 2H), 6.90 (d, J=8.8 Hz, 2H), 6.27 (s, 1H), 5.35 (s, 2H), 4.13 (q, J=7.1 Hz, 2H), 3.83 (s, 2H), 3.78 (s, 3H), 3.72-3.67 (m, 3H), 1.47 (s, 6H), 1.41 (t, J=7.0 Hz, 3H). ES-LCMS m/z 601 (M+H).

Workup

  1. concentrationthe mixture was concentrated
  2. customto give the residue which
  3. extractionextracted with DCM (20 mL×2)
  4. washThe combined organic extracts were washed with brine (20 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-2fc99bb8ed9740baa793e40e73430d75
Source dataset
uspto-grants-2016_07
Patent number
US09382238B2

Reaction notes

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