Diisopropylethylamine → HCID 71493492, compound

HRID 1465893Notes

Reaction equation

HRID 1465893 reaction equation
[Cl:1][C:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][C:5]([C:12]2[N:16]=[CH:15][N:14](/[CH:17]=[CH:18]\[C:19]([OH:21])=O)[N:13]=2)=[CH:4][C:3]=1[C:22]([F:25])([F:24])[F:23].[NH:26]([C:28]1[CH:33]=[N:32][CH:31]=[CH:30][N:29]=1)[NH2:27].C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC.CCN(C(C)C)C(C)C>C1COCC1.CCOC(C)=O>[Cl:1][C:2]1[C:7]([C:8]([F:10])([F:9])[F:11])=[CH:6][C:5]([C:12]2[N:16]=[CH:15][N:14](/[CH:17]=[CH:18]\[C:19]([NH:27][NH:26][C:28]3[CH:33]=[N:32][CH:31]=[CH:30][N:29]=3)=[O:21])[N:13]=2)=[CH:4][C:3]=1[C:22]([F:24])([F:25])[F:23]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 14878232-HydrazinopyrazineHCID 86730373HCID 86730373, compound

Product 1

HCID 71493492HCID 71493492, compoundYield 30.3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-70 °C

Procedure

In a 50-mL, 3-necked, round-bottomed flask charged with a solution of (Z)-3-(3-(4-chloro-3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acrylic acid (0.8 g) in 1:1 EtOAc:THF (20 mL). The solution was cooled to −70° C. and treated sequentially with 2-hydrazinopyrazine (0.275 g, 1.2 eq.), T3P (50% in EtOAc; 2.5 mL, 2.0 eq.) and DIPEA (1.44 mL, 4.0 eq.), added dropwise. The clear reaction mixture was stirred at −60° C. for 1 h before being concentrated under reduced pressure (25° C., 20 mm Hg) to afford crude compound. Purification by column chromatography using (60/120 mesh SiO2, elution with 3-4% MeOH in CH2Cl2) afforded 0.30 g (yield: 30%) (Z)-3-(3-(4-chloro-3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)-N′-(pyrazin-2-yl)acrylohydrazide. 1H NMR (400 MHz, DMSO-d6) δ=10.53 (s, 1H), 9.58 (s, 1H), 9.11 (s, 1H), 8.47 (s, 1H), 8.32 (s, 1H), 8.13 (s, 1H), 8.06 (s, 1H), 7.97 (s, 1H), 7.52-7.55 (d, J=10.4 Hz, 1H), 6.08-6.11 (d, J=10.4 Hz, 1H); LCMS for C17H11ClF6N7O [M+H]+ 478.76. found 478.1 (RT 2.64 min, purity: 100%).

Workup

  1. additionadded dropwise
  2. concentrationbefore being concentrated under reduced pressure (25° C., 20 mm Hg)
  3. customto afford crude compound
  4. customPurification by column chromatography
  5. wash(60/120 mesh SiO2, elution with 3-4% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-8005805259aa48009c0d46db3f84a308
Source dataset
uspto-grants-2015_04
Patent number
US08999996B2

Reaction notes

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