Diisopropylethylamine → HCID 71493150, compound

HRID 1500365Notes

Reaction equation

HRID 1500365 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.[Cl:25][C:26]1[CH:31]=[C:30]([NH:32][NH2:33])[N:29]=[CH:28][N:27]=1.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC.CCN(C(C)C)C(C)C>CCOC(C)=O.CO.C(Cl)Cl>[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]([NH:33][NH:32][C:30]3[CH:31]=[C:26]([Cl:25])[N:27]=[CH:28][N:29]=3)=[O:22])[N:14]=2)[CH:6]=[C:7]([C:9]([F:11])([F:12])[F:10])[CH:8]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 2472224-Chloro-6-hydrazinylpyrimidineHCID 86703006(Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acrylic acid

Product 1

HCID 71493150HCID 71493150, compoundYield 37.8%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
-40 °C

Procedure

A 25-mL, 3-necked, round-bottomed flask was charged with a solution of (Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acrylic acid (0.5 g) and 4-chloro-6-hydrazinopyrimidine (0.20 g, 1.0 eq.) in EtOAc (5.0 mL). The mixture was cooled at −40° C. and treated with T3P (2.3 mL, 2.5 eq.) and DIPEA (0.98 mL, 4.0 eq.). TLC analysis (using 5% MeOH—CH2Cl2 as eluent) showed that the starting material was consumed after 30 min. The reaction mixture was then diluted with CH2Cl2, washed with water, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure (25° C., 20 mmHg) to afford crude material that was subjected to preparative TLC purification using 5% MeOH—CH2Cl2 with as the mobile phase. This afforded 250 mg (yield: 36.74%) (Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)-N′-(6-chloropyrimidin-4-yl-)acrylohydrazide. 1H NMR (400 MHz, DMSO-d6), δ=10.59 (br s, exchangeable, 1H), 9.85 (br s, exchangeable, 1H), 9.52 (s, 1H), 8.50 (s, 2H), 8.38 (s, 1H), 8.27 (s, 1H), 7.52-7.55 (d, 1H, J=10.4 Hz), 6.69 (s, 1H), 6.05-6.08 (d, 1H, J=10.4 Hz); LCMS: Calculated for C17H11ClF6N7O (M+H)+478.76; found: 478.09 (RT 2.79 min, purity: 97.51%).

Workup

  1. customwas consumed after 30 min
  2. additionThe reaction mixture was then diluted with CH2Cl2
  3. washwashed with water
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure (25° C., 20 mmHg)
  7. customto afford crude material that
  8. customwas subjected to preparative TLC purification

Sources & evidence

ORD record
ord-a4a4f5eb77eb4b9c9a9f61c6eba510fe
Source dataset
uspto-grants-2015_12
Patent number
US09206158B2

Reaction notes

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