Ethyl Acetate → HCID 71493322, compound

HRID 1500372Notes

Reaction equation

HRID 1500372 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.[CH2:25]([N:32]1[CH2:37][CH2:36][N:35]([NH2:38])[CH2:34][CH2:33]1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.CCOC(C)=O.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC>CCN(C(C)C)C(C)C.C(Cl)Cl.CO>[CH2:25]([N:32]1[CH2:33][CH2:34][N:35]([NH:38][C:20](=[O:21])/[CH:19]=[CH:18]\[N:15]2[CH:16]=[N:17][C:13]([C:5]3[CH:4]=[C:3]([C:2]([F:24])([F:1])[F:23])[CH:8]=[C:7]([C:9]([F:11])([F:10])[F:12])[CH:6]=3)=[N:14]2)[CH2:36][CH2:37]1)[C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 111923Propylphosphonic anhydrideHCID 121984534-Benzylpiperazin-1-amineHCID 86703006(Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acrylic acid

Product 1

HCID 71493322HCID 71493322, compoundYield 7.3%

Reagents, catalysts & solvents 3

HCID 81531DiisopropylethylamineCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

A 50-mL, 3-necked, round-bottomed flask was charged with (Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acrylic acid (0.220 g, 1.2 eq.), 4-benzylpiperazin-1-amine (0.10 g, 1.0 eq.) and EtOAc (15 ml). T3P (50% in EtOAc 0.99 g, 3.0 eq.) and DIPEA (0.27 mg, 4.0 eq.) were added under nitrogen atmosphere to the cold (−60° C.) solution. The progress of the reaction was followed by TLC analysis (SiO2, 15% MeOH:CH2Cl2 as mobile phase, visualization under UV light). The reaction mixture was quenched in water and extracted with ethyl acetate (3×15 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure (25° C., 20 mmHg) to afford 0.35 g of crude solid. Purification on Combi-flash (eluting with 10% MeOH/CH2Cl2) afforded 20 mg (yield: 6%) (Z)—N-(4-benzylpiperazin-1-yl)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acrylamide. 1H NMR (400 MHz, DMSO-d6) δ 9.44-9.48 (t, 3H), 9.10 (s, 1H), 8.51 (s, 2H), 7.23-7.41 (m, 6H), 6.46-6.49 (d, J=10.4 Hz, 1H), 5.83-5.86 (d, J=10.4 Hz, 1H), 3.47 (s, 2H), 2.81 (s, 4H), 2.23-2.33 (d, 2H) LCMS for C24H23F6N6O [M+H]+ 525.47; found 525.20 (RT 9.87 min, purity: 100%).

Workup

  1. customThe reaction mixture was quenched in water
  2. extractionextracted with ethyl acetate (3×15 mL)
  3. dry with materialThe combined organic extracts were dried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure (25° C., 20 mmHg)
  6. customto afford 0.35 g of crude solid
  7. customPurification
  8. washon Combi-flash (eluting with 10% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-3818132b83994a37b7eb3f0583228b42
Source dataset
uspto-grants-2015_12
Patent number
US09206158B2

Reaction notes

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