Diisopropylethylamine → HCID 86703013, compound

HRID 1777227Notes

Reaction equation

HRID 1777227 reaction equation
[F:1][C:2]([F:24])([F:23])[C:3]1[CH:4]=[C:5]([C:13]2[N:17]=[CH:16][N:15](/[CH:18]=[CH:19]\[C:20](O)=[O:21])[N:14]=2)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[CH3:25][CH:26]1[N:31]([CH2:32][C:33]([NH:35][NH2:36])=[O:34])[CH:30]([CH3:37])[CH2:29][O:28][CH2:27]1.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC.CCN(C(C)C)C(C)C>C1COCC1.O>[F:24][C:2]([F:23])([F:1])[C:3]1[CH:4]=[C:5]([C:13]2[N:17]=[CH:16][N:15](/[CH:18]=[CH:19]\[C:20]([NH:36][NH:35][C:33](=[O:34])[CH2:32][N:31]3[CH:26]([CH3:25])[CH2:27][O:28][CH2:29][CH:30]3[CH3:37])=[O:21])[N:14]=2)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 86703006(Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acrylic acidHCID 86703014HCID 86703014, compound

Product 1

HCID 86703013HCID 86703013, compoundYield 7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To the solution of (Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acrylic acid (0.2 g, 0.569 mmol) and 2-(3,5-dimethylmorpholino)acetohydrazide (0.106 g, 0.569 mmol) in THF (10 mL) were added T3P (0.543 g, 0.854 mmol) followed by DIPEA (0.110 g, 0.854 mmol) at −60° C. and stirred for 2 h. The reaction mixture was transferred into 25 mL iced-water and extracted with ethyl acetate (2×25 mL) and the combined organic layers was washed with brine, dried over anhydrous sodium sulphate, and concentrated under reduced pressure to afford the crude product, which was purified by chromatography (0-3% MeOH/CH2Cl2) to give 0.02 g of (Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)-N′-(2-(3,5-dimethylmorpholino)acetyl)acrylohydrazide (Yield: 7%). 1H NMR (400 MHz, DMSO-d6) δ 10.58 (s, 1H), 9.83 (s, 1H), 9.56 (s, 1H), 8.54-8.56 (m, 2H), 8.25-8.30 (m, 1H), 7.49-7.51 (d, J=10.4 Hz, 1H)), 6.01-6.04 (d, J=10.4 Hz, 1H), 3.44-3.57 (m, 2H), 3.28-3.34 (m, 2H), 3.21 (s, 1H), 3.15 (s, 1H), 2.84-2.88 (m, 2H), 0.93-1.04 (m, 6H): LCMS m/z 521.18 [M+H]+, tR 1.898 min.

Workup

  1. extractionextracted with ethyl acetate (2×25 mL)
  2. washthe combined organic layers was washed with brine
  3. dry with materialdried over anhydrous sodium sulphate
  4. concentrationconcentrated under reduced pressure
  5. customto afford the crude product, which
  6. customwas purified by chromatography (0-3% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-3f65d58e1373457ebe789e4f7789c737
Source dataset
uspto-grants-2016_02
Patent number
US09266843B2

Reaction notes

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