Diisopropylethylamine → HCID 71494895, compound

HRID 1487021Notes

Reaction equation

HRID 1487021 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.[F:25][C:26]1([CH2:30][N:31]([CH3:33])[CH3:32])[CH2:29][NH:28][CH2:27]1.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC.CCN(C(C)C)C(C)C>C(Cl)Cl>[F:24][C:2]([F:23])([F:1])[C:3]1[CH:4]=[C:5]([C:13]2[N:17]=[CH:16][N:15](/[CH:18]=[CH:19]\[C:20]([N:28]3[CH2:29][C:26]([CH2:30][N:31]([CH3:33])[CH3:32])([F:25])[CH2:27]3)=[O:21])[N:14]=2)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 86703006(Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acrylic acidHCID 894018153-Azetidinemethanamine, 3-fluoro-N,N-dimethyl-

Product 1

HCID 71494895HCID 71494895, compoundYield 3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-60 °C

Procedure

(Z)-3-(3-(3,5-Bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acrylic acid (0.50 g, 1.0 eq.) was dissolved in DCM (10 mL). The reaction mixture was cooled to −60° C., at which temperature 1-(3-fluoroazetidin-3-yl)-N,N-dimethylmethanamine (0.22 g, 1.2 eq) and T3P (50% in EtOAc) (1.08 g, 1.2 eq.) were added, followed by DIPEA (0.36 g, 2 eq.). The clear reaction mixture was stirred at −60° C. for 45 min. The reaction mixture was concentrated under reduced pressure (25° C., 20 mm Hg) to afford the crude product, which was purified by chromatography to give 12 mg of (Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)-1-(3-((dimethylamino)methyl)-3-fluoroazetidin-1-yl)prop-2-en-1-one (3% yield). 1H NMR (400 MHz, CDCl3) δ=9.75 (s, 1H), 8.62 (s, 2H), 7.94 (s, 1H), 7.24-7.21 (d, J=10.8 Hz, 1H), 5.69-5.66 (d, J=10.8 Hz, 1H), 4.37-4.25 (m, 2H), 4.22-4.15 (m, 2H), 2.82-2.76 (d, 2H), 2.35 (s, 2.35, 1H); LCMS for C19H19F7N5O [M+H]+ 466.4 found 466.3 at retention time 2.263 min

Workup

  1. additionwere added
  2. concentrationThe reaction mixture was concentrated under reduced pressure (25° C., 20 mm Hg)
  3. customto afford the crude product, which
  4. customwas purified by chromatography

Sources & evidence

ORD record
ord-524405ff7298404fbddb917e237fc406
Source dataset
uspto-grants-2016_08
Patent number
US09428490B2

Reaction notes

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