Diisopropylethylamine → HCID 71493808, compound

HRID 1486985Notes

Reaction equation

HRID 1486985 reaction equation
[CH3:1][NH:2][CH2:3][C:4]1[CH:5]=[N:6][C:7]([CH3:10])=[N:8][CH:9]=1.[F:11][C:12]([F:34])([F:33])[C:13]1[CH:14]=[C:15]([C:23]2[N:27]=[CH:26][N:25](/[CH:28]=[CH:29]\[C:30]([OH:32])=O)[N:24]=2)[CH:16]=[C:17]([C:19]([F:22])([F:21])[F:20])[CH:18]=1.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC.CCN(C(C)C)C(C)C>ClCCl.CO>[F:34][C:12]([F:11])([F:33])[C:13]1[CH:14]=[C:15]([C:23]2[N:27]=[CH:26][N:25](/[CH:28]=[CH:29]\[C:30]([N:2]([CH3:1])[CH2:3][C:4]3[CH:5]=[N:6][C:7]([CH3:10])=[N:8][CH:9]=3)=[O:32])[N:24]=2)[CH:16]=[C:17]([C:19]([F:22])([F:21])[F:20])[CH:18]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 22929643N-Methyl-1-(2-methylpyrimidin-5-yl)methanamineHCID 86703006(Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acrylic acid

Product 1

HCID 71493808HCID 71493808, compoundYield 4.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent3×

Conditions

Temperature
-20 °C

Procedure

In a 25 mL, 3N round-bottomed flask equipped with nitrogen inlet, N-methyl-1-(2-methylpyrimidin-5-yl)methanamine (1) (0.1 g, 1.0 eq.) and (Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acrylic acid (0.178 g, 0.7 eq.) was charged along with dichloromethane (2 mL, 10 V). The reaction mixture was cooled to −20° C. and then added T3P (50% in EtOAc) (0.550 mL, 1.2 eq.) followed by DIPEA (0.250 mL, 2 eq.) was added to reaction mixture. The clear reaction mixture was stirred at −20° C. for 30 min. The progress of the reaction was followed by TLC analysis on silica gel with 5% Methanol in dichloromethane as mobile phase and visualization with UV, which shows that starting material was consumed after 30 min stirring at −30° C. Reaction mixture was diluted by dichloromethane wash with water (2×10 mL), organic layer dried over sodium sulfate and concentrated by rotary evaporation (25° C., 20 mm Hg) to afford crude compound (0.2 g). The crude reaction mixture was purified by column chromatography using 60/120 mesh silica and methanol: dichloromethane as mobile phase. The column was packed in dichloromethane and started eluting in MeOH in gradient manner starting with fraction collection (500 mL fractions). The compound started eluting from 2% methanol in dichloromethane. Fractions containing such TLC profile were collected together to obtain pure compound 0.01 g Yield (4.19%).

Workup

  1. customIn a 25 mL, 3N round-bottomed flask equipped with nitrogen inlet
  2. additionwas added to reaction mixture
  3. customwas consumed after 30 min
  4. stirringstirring at −30° C
  5. customReaction mixture
  6. washwash with water (2×10 mL), organic layer
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated by rotary evaporation (25° C., 20 mm Hg)
  9. customto afford crude compound (0.2 g)
  10. customThe crude reaction mixture
  11. customwas purified by column chromatography
  12. washstarted eluting in MeOH in gradient manner
  13. customstarting with fraction collection (500 mL fractions)
  14. washThe compound started eluting from 2% methanol in dichloromethane
  15. additionFractions containing such TLC profile
  16. customwere collected together

Sources & evidence

ORD record
ord-9b1e41f339c04f2da63f2c1b15b7086d
Source dataset
uspto-grants-2016_08
Patent number
US09428490B2

Reaction notes

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