Ethyl Acetate → HCID 178465998, compound

HRID 1050178Notes

Reaction equation

HRID 1050178 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]([OH:29])=O)=[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].[F:31][C:32]([F:43])([F:42])[C:33]([C:36]1[CH:40]=[C:39]([NH2:41])[NH:38][N:37]=1)([CH3:35])[CH3:34].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:41][C:39]3[NH:38][N:37]=[C:36]([C:33]([CH3:35])([CH3:34])[C:32]([F:43])([F:42])[F:31])[CH:40]=3)=[O:29])=[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 178439405HCID 178439405, compound

Product 1

HCID 178465998HCID 178465998, compoundYield 42.1%

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 (100 mg, 0.243 mmol) and 3-(1,1,1-trifluoro-2-methylpropan-2-yl)-1H-pyrazol-5-amine (51.6 mg, 0.267 mmol) in pyridine (3 mL) was added T3P® (EA solvate) (0.3 mL, 0.243 mmol) at 25° C. Then the mixture was stirred for 2 h, the mixture was concentrated to give a 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-(3-(1,1,1-trifluoro-2-methylpropan-2-yl)-1H-pyrazol-5-yl)acetamide (100 mg, 0.102 mmol, 42.1% yield): 1H NMR (400 MHz, CD3OD) δ 8.52 (d, J=4.2 Hz, 1H), 7.93 (d, J=2.0 Hz, 1H), 7.48-7.33 (m, 6H), 6.90 (d, J=8.6 Hz, 2H), 5.35 (s, 2H), 4.19-4.09 (m, 2H), 3.78 (s, 3H), 3.70-3.63 (m, 2H), 1.54-1.36 (m, 9H). ES-LCMS m/z 587 (M+H).

Workup

  1. concentrationthe mixture was concentrated
  2. customto give a 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-c22360f3e8354c8ab6497fe10775a93a
Source dataset
uspto-grants-2016_07
Patent number
US09382238B2

Reaction notes

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