Diisopropylethylamine → HCID 72201374, compound

HRID 1777223Notes

Reaction equation

HRID 1777223 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]([OH:22])=O)[N:14]=2)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[O:25]1[CH2:30][CH2:29][N:28]([C:31](=[O:36])[C:32]([NH:34][NH2:35])=[O:33])[CH2:27][CH2:26]1.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC.CCN(C(C)C)C(C)C>C1COCC1.O>[F:10][C:9]([F:11])([F:12])[C:7]1[CH:6]=[C:5]([C:13]2[N:17]=[CH:16][N:15](/[CH:18]=[CH:19]\[C:20]([NH:35][NH:34][C:32](=[O:33])[C:31]([N:28]3[CH2:29][CH2:30][O:25][CH2:26][CH2:27]3)=[O:36])=[O:22])[N:14]=2)[CH:4]=[C:3]([C:2]([F:1])([F:23])[F:24])[CH:8]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 4358478HCID 4358478, compoundHCID 86703006(Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acrylic acid

Product 1

HCID 72201374HCID 72201374, compoundYield 169.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-60 °C

Procedure

A 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-morpholino-2-oxoacetohydrazide (0.02 g, 0.175 mmol) in THF (3 mL) was cooled to −60° C. T3P (0.098 g, 0.569 mmol) (0.50 mL) was added dropwise followed by DIPEA (0.11 g, 0.854 mmol) and stirred at −60° C. for 1 h. The reaction mixture was transferred into 25 mL of iced water and extracted with ethyl acetate (2×25 mL). Combined organic layers were washed with brine, dried over anhydrous sodium sulphate, and concentrated under reduced pressure to give 0.3 g of crude product, which was purified by chromatography (0-4% MeOH/CH2Cl2) to give 0.15 g of (Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)-N′-(2-morpholino-2-oxoacetyl) acrylohydrazide (Yield 50%). NMR (400 MHz, DMSO-d6) δ 10.70-10.88 (m, 2H), 9.56 (s, 1H), 8.57 (s, 2H), 8.29 (s, 1H), 7.52-7.55 (d, J=10.4 Hz, 1H), 6.0-6.03 (d, J=10.4 Hz, 1H), 3.51-3.64 (m, 8H). LCMS m/z 507.25 [M+H]+, tR=2.012 min.

Workup

  1. extractionextracted with ethyl acetate (2×25 mL)
  2. washCombined organic layers were washed with brine
  3. dry with materialdried over anhydrous sodium sulphate
  4. concentrationconcentrated under reduced pressure
  5. customto give 0.3 g of crude product, which
  6. customwas purified by chromatography (0-4% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-f770063aac4f42bd8960a0f29f1c2686
Source dataset
uspto-grants-2016_02
Patent number
US09266843B2

Reaction notes

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